lenalidomide 10 MG Oral Capsule

INDICATIONS AND USAGE Lenalidomide capsules are a thalidomide analogue indicated for the treatment of adult patients with: • Multiple myeloma (MM), in combination with dexamethasone ( 1.1 ). • MM, as maintenance following autologous hematopoietic stem cell transplantation (auto-HSCT) ( 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 ). • Mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib ( 1.3 ). • Previously treated follicular lymphoma (FL), in combination with a rituximab product ( 1.4 ). • Previously treated marginal zone lymphoma (MZL), in combination with a rituximab product ( 1.5 ). 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). Lenalidomide capsules are indicated as maintenance therapy in adult patients with MM following autologous hematopoietic stem cell transplantation (auto-HSCT). 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. 1.3 Mantle Cell Lymphoma Lenalidomide capsules are indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. 1.4 Follicular Lymphoma Lenalidomide capsules in combination with a rituximab product, are indicated for the treatment of adult patients with previously treated follicular lymphoma (FL). 1.5 Marginal Zone Lymphoma Lenalidomide capsules in combination with a rituximab product, are indicated for the treatment of adult patients with previously treated marginal zone lymphoma (MZL). 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) ] .

DOSAGE AND ADMINISTRATION 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 ). MCL: 25 mg once daily orally on Days 1 to 21 of repeated 28-day cycles ( 2.3 ). 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 or unacceptable toxicity. For patients who are auto-HSCT-eligible, hematopoietic stem cell mobilization should occur 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 38.5ºC) Interrupt lenalidomide capsules treatment Return to at least 500/mcL Resume lenalidomide capsules at 2.5 mg daily 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 f

WARNINGS AND PRECAUTIONS Increased Mortality: serious and fatal cardiac adverse reactions occurred in patients with CLL treated with lenalidomide capsules ( 5.5 ). Second Primary Malignancies (SPM): Higher incidences of SPM were observed in controlled trials of patients with MM receiving lenalidomide capsules ( 5.6 ). Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue ( 5.7 ). Hepatotoxicity: Hepatic failure including fatalities; monitor liver function. Stop lenalidomide capsules and evaluate if hepatotoxicity is suspected ( 5.8 ). Severe Cutaneous Reactions: Discontinue lenalidomide for severe reactions ( 5.9 ). Tumor lysis syndrome (TLS) including fatalities: Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions ( 5.10 ). Tumor flare reaction: Serious tumor flare reactions, including fatal reactions, have occurred during investigational use of lenalidomide capsules for chronic lymphocytic leukemia and lymphoma ( 5.11 ). Impaired Stem Cell mobilization: A decrease in the number of CD34+ cells collected after treatment (> 4 cycles) with lenalidomide has been reported. Consider early referral to transplant center ( 5.12 ). Early mortality in MCL: Higher rate of early deaths have occurred in patients with MCL ( 5.14 ). Hypersensitivity: Monitor patients for potential hypersensitivity. Discontinue lenalidomide for angioedema and anaphylaxis ( 5.15 ). 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. 5.2 Lenalidomide REMS Program Because of the embryo-fetal risk [see Warnings and Precautions ( 5.1 )] , lenalidomide capsules are available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the Lenalidomide REMS program. Required components of the Lenalidomide REMS program include the following: Prescribers must be certified with the Lenalidomide REMS program by enrolling and complying with the REMS requirements. Patients must sign a Patient-Physician agreement form and comply with the REMS requirements. In particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations ( 8.3 )] and males must comply with contraception requirements [see Use in Specific Populations ( 8.3 )] . Pharmacies must be certified with the Lenalidomide REMS program, must only dispense to patients who are authorized to receive lenalidomide capsules and comply with REMS requirements. Further information about the Lenalidomide REMS program is available at www.lenalidomiderems.com or by telephone at 1-888-423-5436. 5.3 Hematologic Toxicity Lenalidomide capsules can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medication that may increase risk of bleeding. Patients taking lenalidomide capsules should have their complete blood counts assessed periodically as described below [see Dosage and Administration ( 2.1 , 2.2 , 2.3 )] . Monitor complete blood counts (CBC) in patients taking lenalidomide capsules in combination with dexamethasone for MM every 7 days (weekly) for the first 2 cycles, on Days 1 and 15 of Cycle 3, and every 28 days (4 weeks) thereafter. A dose interruption and/or dose reduction may be required [see Dosage and Administration ( 2.1 )] . In trials for another indication, Grade 3 or 4 neutropenia was reported in up to 59% of lenalidomide capsules-treated patients and Grade 3 or 4 thrombocytopenia in up to 38% of lenalidomide capsules-treated patients. Monitor complete blood counts (CBC) in patients taking lenalidomide capsules for MDS weekly for the first 8 weeks and at least monthly thereafter. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the MDS study. In the 48% of patients who developed Grade 3 or 4 neutropenia, the median time to onset was 42 days (range, 14 to 411 days), and the median time to documented recovery was 17 days (range, 2 to 170 days). In the 54% of patients who developed Grade 3 or 4 thrombocytopenia, the median time to onset was 28 days (range, 8 to 290 days), and the median time to documented recovery was 22 days (range, 5 to 224 days) [see Boxed Warning and Dosage and Administration ( 2.2 )] . Monitor complete blood counts (CBC) in patients taking lenalidomide capsules for MCL weekly for the first cycle (28 days), every 2 weeks during cycles 2 to 4, and then monthly thereafter. Patients may require dose interruption and/or dose reduction. In the MCL trial, Grade 3 or 4 neutropenia was reported in 43% of the patients. Grade 3 or 4 thrombocytopenia was reported in 28% of the patients. 5.4 Venous and Arterial Thromboembolism Venous thromboembolic events (VTE [DVT and PE]) and arterial thromboembolic events (ATE, myocardial infarction and stroke) are increased in patients treated with lenalidomide. A significantly increased risk of DVT (7.4%) and of PE (3.7%) occurred in patients with MM after at least one prior therapy who were treated with lenalidomide and dexamethasone therapy compared to patients treated in the placebo and dexamethasone group (3.1% and 0.9%) in clinical trials with varying use of anticoagulant therapies. In the newly diagnosed multiple myeloma (NDMM) study in which nearly all patients received antithrombotic prophylaxis, DVT was reported as a serious adverse reaction (3.6%, 2.0%, and 1.7%) in the Rd Continuous, Rd18, and MPT Arms, respectively. Th

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

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Lenalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of lenalidomide are mediated through its target cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex. In vitro , in the presence of drug, substrate proteins (including Aiolos, Ikaros, and CK1α) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects. Lenalidomide inhibits proliferation and induces apoptosis of certain hematopoietic tumor cells including MM, mantle cell lymphoma, and del (5q) myelodysplastic syndromes, follicular lymphoma and marginal zone lymphoma in vitro . Lenalidomide causes a delay in tumor growth in some in vivo nonclinical hematopoietic tumor models including MM. Immunomodulatory properties of lenalidomide include increased number and activation of T cells and natural killer (NK) cells leading to direct and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) via increased secretion of interleukin-2 and interferon-gamma, increased numbers of NKT cells, and inhibition of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. In MM cells, the combination of lenalidomide and dexamethasone synergizes the inhibition of cell proliferation and the induction of apoptosis. The combination of lenalidomide and rituximab increases ADCC and direct tumor apoptosis in follicular lymphoma cells and increases ADCC in marginal zone lymphoma cells compared to rituximab alone in vitro . 12.2 Pharmacodynamics Cardiac Electrophysiology The effect of lenalidomide on the QTc interval was evaluated in 60 healthy male subjects in a thorough QT study. At a dose two times the maximum recommended dose, lenalidomide did not prolong the QTc interval. The largest upper bound of the two-sided 90% CI for the mean differences between lenalidomide and placebo was below 10 ms. 12.3 Pharmacokinetics Absorption Following single and multiple doses of lenalidomide in patients with MM or MDS, the maximum plasma concentrations occurred between 0.5 and 6 hours post-dose. The single and multiple dose pharmacokinetic disposition of lenalidomide is linear with AUC and C max values increasing proportionally with dose. Multiple doses of lenalidomide at the recommended dosage does not result in drug accumulation. Administration of a single 25 mg dose of lenalidomide with a high-fat meal in healthy subjects reduces the extent of absorption, with an approximate 20% decrease in AUC and 50% decrease in C max . In the trials where the efficacy and safety were established for lenalidomide, the drug was administered without regard to food intake. Lenalidomide capsules can be administered with or without food. The oral absorption rate of lenalidomide in patients with MCL is similar to that observed in patients with MM or MDS. Distribution In vitro [ 14 C]-lenalidomide binding to plasma proteins is approximately 30%. Lenalidomide is present in semen at 2 hours (1379 ng/ejaculate) and 24 hours (35 ng/ejaculate) after the administration of lenalidomide capsules 25 mg daily. Elimination The mean half-life of lenalidomide is 3 hours in healthy subjects and 3 to 5 hours in patients with MM, MDS or MCL. Metabolism Lenalidomide undergoes limited metabolism. Unchanged lenalidomide is the predominant circulating component in humans. Two identified metabolites are 5-hydroxy-lenalidomide and N-acetyl-lenalidomide; each constitutes less than 5% of parent levels in circulation. Excretion Elimination is primarily renal. Following a single oral administration of [ 14 C]-lenalidomide 25 mg to healthy subjects, approximately 90% and 4% of the radioactive dose was eliminated within ten days in urine and feces, respectively. Approximately 82% of the radioactive dose was excreted as lenalidomide in the urine within 24 hours. Hydroxy-lenalidomide and N-acetyl-lenalidomide represented 4.6% and 1.8% of the excreted dose, respectively. The renal clearance of lenalidomide exceeds the glomerular filtration rate. Specific Populations Renal Impairment: Eight subjects with mild renal impairment (creatinine clearance (CLcr) 50 to 79 mL/min calculated using Cockcroft-Gault), 9 subjects with moderate renal impairment (CLcr 30 to 49 mL/min), 4 subjects with severe renal impairment (CLcr < 30 mL/min), and 6 patients with end stage renal disease (ESRD) requiring dialysis were administered a single 25 mg dose of lenalidomide. Three healthy subjects of similar age with normal renal function (CLcr > 80 mL/min) were also administered a single 25 mg dose of lenalidomide. As CLcr decreased, half-life increased and drug clearance decreased linearly. Patients with moderate and severe impairment had a 3-fold increase in half-life and a 66% to 75% decrease in drug clearance compared to healthy subjects. Patients on hemodialysis (n=6) had an approximate 4.5-fold increase in half-life and an 80% decrease in drug clearance compared to healthy subjects. Approximately 30% of the drug in body was removed during a 4-hour hemodialysis session. Adjust the starting dose of lenalidomide capsules in patients with renal impairment based on the CLcr value [see Dosage and Administration (2.6) ] . Hepatic Impairment: Mild hepatic impairment (defined as total bilirubin > 1 to 1.5 times upper limit normal (ULN) or any aspartate transaminase greater than ULN) did not influence the disposition of lenalidomide. No pharmacokinetic data is available for patients with moderate to severe hepatic impairment. Other Intrinsic Factors: Age (39 to 85 years), body weight (33 to 135 kg), sex, race, and type of hematological malignancies (MM, MDS or MCL) did not have a clinically relevant effect on lenalidomide clearance in adult patients. Drug Interactions Co-administration of a single dose or multiple doses of dexamethasone (40 mg) had no clinically relevant effect on the multiple dose pharmacokinetics of lenalidomide capsules (25 mg). Co-administration of lenalidomide capsules (25 mg) after multiple doses of a P-gp inhibitor such as quinidine (600 mg twice daily) did not significantly increase the C max or AUC of lenalidomide. Co-administration of the P-gp inhibitor and substrate temsirolimus (25 mg), with lenalidomide capsules (25 mg) did not significantly alter the pharmacokinetics of lenalidomide, temsirolimus, or sirolimus (metabolite of temsirolimus). In vitro studies demonstrated that lenalidomide is a substrate of P-glycoprotein (P-gp). Lenalidomide is not a substrate of human breast cancer resistance protein (BCRP), multidrug resistance protein (MRP) transporters MRP1, MRP2, or MRP3, organic anion transporters (OAT) OAT1 and OAT3, organic anion transporting polypeptide 1B1 (OATP1B1), organic cation transporters (OCT) OCT1 and OCT2, multidrug and toxin extrusion protein (MATE) MATE1, and organic cation transporters novel (OCTN) OCTN1 and OCTN2. Lenalidomide is not an inhibitor of P-gp, bile salt export pump (BSEP), BCRP, MRP2, OAT1, OAT3, OATP1B1, OATP1B3, or OCT2. Lenalidomide does not inhibit or induce CYP450 isoenzymes. Also, lenalidomide does not inhibit bilirubin glucuronidation formation in human liver microsomes with UGT1A1 genotyped as UGT1A1*1/*1, UGT1A1*1/*28, and UGT1A1*28/*28.