Class: Immunologic agent
- Capsules, oral 2.5 mg
- Capsules, oral 5 mg
- Capsules, oral 10 mg
- Capsules, oral 15 mg
- Capsules, oral 25 mg
Possesses antineoplastic, immunomodulatory, and antiangiogenic properties. Inhibits the secretion of proinflammatory cytokines.
Rapidly absorbed following oral administration, with C max occurring 0.5 to 6 h postdose. Food reduces C max and AUC by 50% and 20%, respectively. The pharmacokinetic disposition is linear; C max and AUC increase proportionately with dose.
Plasma protein binding is approximately 30%.
Undergoes limited metabolism. Unchanged drug is predominant in circulation, with metabolites, hydroxy-lenalidomide and N-acetyl-lenalidomide, each constituting less than 5% of parent levels in circulation.
82% and 90% of a dose are eliminated renally within 24 h and 10 days, respectively. Renal Cl exceeds glomerular filtration rate. The half-life is about 3 to 5 h.
Special PopulationsRenal Function Impairment
The AUC was 56% greater in patients with multiple myeloma with mild renal impairment compared with those with normal renal function. There is a 3-fold increase in half-life and a 66% to 75% decrease in drug Cl in patients with moderate and severe renal impairment compared with healthy subjects. Hemodialysis patients had a 4.5-fold increase in half-life and an 80% decrease in drug Cl compared with healthy subjects. 40% of a dose can be removed during a single dialysis session.Hepatic Function Impairment
Pharmacokinetics have not been studied in patients with hepatic impairment.Elderly
Effects of age on pharmacokinetics have not been studied.Children
Data are not available in patients younger than 18 y.Gender
Effects of gender on pharmacokinetics have not been studied.Race
Effects of race on pharmacokinetics have not been studied.
Indications and Usage
Treatment of patients with transfusion-dependent anemia due to low- or intermediate-1–risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality, with or without additional cytogenetic abnormalities; treatment of multiple myeloma in combination with dexamethasone in patients who have received at least 1 prior therapy.
Behçet syndrome; multiple myeloma (induction therapy).
Pregnancy; hypersensitivity to any component of the product.
Dosage and AdministrationMyelodysplastic Syndromes
PO 10 mg once daily.Dosage adjustments due to thrombocytopenia If thrombocytopenia develops within 4 wk of starting treatment at 10 mg once daily If baseline platelet counts 100,000/mcL or more
Interrupt lenalidomide when platelets fall to fewer than 50,000/mcL; then resume lenalidomide at 5 mg once daily when platelets return to 50,000/mcL or more.If baseline platelet counts less than 100,000/mcL
Interrupt lenalidomide when platelets fall to 50% of baseline value. Resume lenalidomide at 5 mg once daily if baseline is 60,000/mcL or greater and returns to 50,000/mcL or more, or if baseline is less than 60,000/mcL and returns to 30,000/mcL or more.If thrombocytopenia develops after 4 wk of starting treatment at 10 mg once daily
Interrupt lenalidomide when platelets fall to less than 30,000/mcL, or less than 50,000/mcL with platelet transfusions; then resume lenalidomide at 5 mg once daily when platelets return to 30,000/mcL or more (without hemostatic failure).If thrombocytopenia develops during treatment at 5 mg once daily
Interrupt lenalidomide when platelets fall to less than 30,000/mcL, or less than 50,000/mcL with platelet transfusions; then resume lenalidomide at 2.5 mg daily when platelets return to 30,000/mcL or more (without hemostatic failure).Dosage adjustments due to neutropenia If neutropenia develops within 4 wk of starting treatment at 10 mg once daily If baseline absolute neutrophil count 1,000/mcL or more
Interrupt lenalidomide when absolute neutrophil count (ANC) falls to less than 750/mcL; then resume lenalidomide at 5 mg once daily when neutrophils return to 1,000/mcL or more.If baseline ANC less than 1,000/mcL
Interrupt lenalidomide when neutrophils fall to less than 500/mcL; then resume lenalidomide at 5 mg once daily when neutrophils return to 500/mcL or more.If neutropenia develops after 4 wk of starting treatment at 10 mg once daily
Interrupt lenalidomide when neutrophils fall to less than 500/mcL for 7 days or more, or less than 500/mcL and associated with fever (101.3°F or higher); then resume lenalidomide at 5 mg once daily when neutrophils return to 500/mcL or more.If neutropenia develops during treatment at 5 mg once daily
Interrupt lenalidomide when neutrophils fall to less than 500/mcL for 7 days or more, or less than 500/mcL and associated with fever (101.3°F or higher); then resume lenalidomide at 2.5 mg daily when neutrophils return to 500/mcL or more.Dosage adjustments due to other grade 3/4 toxicities
Hold treatment and restart at next lower dose level when toxicity has resolved to grade 2 or less.Multiple Myeloma
PO 25 mg once daily on days 1 to 21 of repeated 28-day cycles in combination with dexamethasone. The recommended dosage of dexamethasone is 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy; then 40 mg/day on days 1 to 4 every 28 days.Dosage adjustments due to thrombocytopenia
Interrupt treatment, follow CBC weekly when platelets fall to less than 30,000/mcL, and resume treatment at 15 mg/day when platelets return to 30,000/mcL or more. Interrupt treatment for each subsequent platelet drop to less than 30,000/mcL, and resume treatment at 5 mg less than the previous dose when platelets return to 30,000/mcL or more. Do not dose below 5 mg daily.Dosage adjustments due to ANC
Interrupt treatment, add granulocyte colony–stimulating factor, and follow CBC weekly when neutrophils fall to less than 1,000/mcL; then resume treatment at 25 mg daily when neutrophils return to 1,000/mcL or more and neutropenia is the only toxicity; however, if there is other toxicity, resume treatment at 15 mg daily. Interrupt treatment for each subsequent drop in neutrophils below 1,000/mcL; then resume treatment at 5 mg less than the previous dose when neutrophils are 1,000/mcL or greater. Do not dose below 5 mg/day.Other grade 3/4 toxicities
For other grade 3/4 toxicities related to lenalidomide, hold treatment and restart at the next lower dose level when toxicity has resolved to grade 2 or less.Renal Function Impairment
PO After initiation of therapy, subsequent dose modification should be based on individual patient treatment tolerance.Multiple myeloma Moderate renal function impairment (CrCl 30 to 60 mL/min)
10 mg every 24 h.Severe renal function impairment (CrCl less than 30 mL/min [not requiring dialysis])
15 mg every 48 h.End-stage renal disease (CrCl less than 30 mL/min [requiring dialysis])
5 mg once daily. On dialysis days, administer the dose following dialysis.Myelodysplastic syndromes Moderate renal function impairment (CrCl 30 to 60 mL/min)
5 mg every 24 h.Severe renal function impairment (CrCl less than 30 mL/min [not requiring dialysis])
2.5 mg every 24 h.End-stage renal disease (CrCl less than 30 mL/min [requiring dialysis])
2.5 mg daily. On dialysis days, administer the dose following dialysis.
- Administer dose once daily with water. Administer without regard to meals but with food if GI upset occurs.
- Instruct patient not to break, chew, or open the capsule.
- If a dose is missed, administer as soon as possible on that day. If the dose is missed for an entire day, administer the next dose at the regularly scheduled time. Do not double the dose to catch up.
Store between 59° and 86°F.
An increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in patients with multiple myeloma who were treated with lenalidomide and dexamethasone. Monitor for signs and symptoms of thromboembolism. Instruct patients to seek medical care if they develop symptoms of shortness of breath.Digoxin
Digoxin C max and AUC increased 14% with coadministration. Periodically monitor digoxin plasma concentrations.Erythropoietic agents (eg, epoetin), estrogen-containing therapies (eg, oral contraceptives)
The risk of venous thromboembolic events may be increased. Use with caution. Monitor for signs and symptoms of thromboembolism. Instruct patients to seek medical care if they develop symptoms of shortness of breath.Food
Administration of lenalidomide with a high-fat meal in healthy subjects decreased the extent of absorption of lenalidomide, decreasing the AUC and C max . However, lenalidomide may be taken without regard to meals.
Hypertension (6%); palpitations (5%); aggravated atrial fibrillation, angina pectoris, aortic disorder, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, cardiogenic shock, cardiomyopathy, cardiorespiratory arrest, CHF, DVT, hypotension, ischemia, MI, myocardial ischemia, PE, superficial thrombophlebitis, supraventricular arrhythmia, tachyarrhythmia, thrombosis, transient ischemic attack, ventricular dysfunction.
Fatigue (31%); pyrexia (21%); dizziness, headache (20%); asthenia (15%); insomnia (10%); hypoesthesia (7%); depression, peripheral neuropathy (5%); abnormal gait, aphasia, cerebellar infarction, cerebral infarction, cerebrovascular accident, confusional state, depressed level of consciousness, dysarthria, migraine, spinal cord compression, subarachnoid hemorrhage.
Pruritus (42%); rash (36%); dry skin (14%); contusion, night sweats (8%); increased sweating (7%); ecchymosis, erythema (5%); acute febrile neutrophilic dermatosis.
Nasopharyngitis (23%); pharyngitis (16%); rhinitis (7%); ear infection, vertigo.
Hypothyroidism (7%); Basedow disease, hypoglycemia.
Diarrhea (49%); constipation, nausea (24%); abdominal pain (12%); anorexia, vomiting (10%); upper abdominal pain (8%); dry mouth (7%); dysgeusia, loose stools (6%); colonic polyp, diverticulitis, dysphagia, gastritis, gastroenteritis, gastroesophageal reflux disease, GI hemorrhage, intestinal perforation, irritable bowel syndrome, ischemic colitis, melena, obstructive inguinal hernia, pancreatitis, pancreatitis due to biliary obstruction, perirectal abscess, rectal hemorrhage, small intestinal obstruction, upper GI hemorrhage.
UTI (11%); dysuria (7%); azotemia, blood creatinine increase, hematuria, kidney infection, renal failure, renal mass, ureteric calculus.
Thrombocytopenia (62%); neutropenia (59%); anemia (12%); leukopenia (8%); febrile neutropenia (5%); bone marrow depression, coagulopathy, Hgb decreased, hemolysis, hemolytic anemia, refractory anemia, splenic infarction, warm-type hemolytic anemia.
Increased ALT (8%); acute cholecystitis, cholecystitis, hepatic failure, hyperbilirubinemia, LFTs abnormal.
Hypokalemia (11%); hypomagnesemia (6%); hypernatremia.
Arthralgia (22%); back pain (21%); muscle cramp (18%); limb pain (11%); myalgia (9%); peripheral swelling (8%); rigors (6%); arthritis, bone fractures, chondrocalcinosis pyrophosphate, gouty arthritis, neck pain.
Cough (20%); dyspnea (17%); epistaxis, upper respiratory tract infection (15%); pneumonia (12%); sinusitis (8%); exertional dyspnea (7%); bronchitis (6%); acute sinusitis, chronic obstructive airway disease exacerbated, interstitial lung disease, lobar pneumonia, lung infiltration, respiratory failure, wheezing.
Peripheral edema (20%); edema (10%); pain (7%); cellulitis, chest pain (5%); bacteremia, central line infection, clostridial infection, dehydration, disease progression, Enterobacter sepsis, fall, fungal infection, gout, herpes viral infection, hypersensitivity, infection, influenza, intermittent pyrexia, Klebsiella sepsis, localized infection, neoplasm (eg, acute leukemia, acute myeloid leukemia, bronchoalveolar carcinoma, lymphoma, metastatic lung cancer, metastatic prostate cancer), nodule, oral infection, overdose, pelvic pain, postprocedural hemorrhage, Pseudomonas infection, road traffic accident, septic shock, staphylococcal infection, sudden death, transfusion reaction, troponin I increased.
WarningsDeep vein thrombosis and pulmonary embolism
Increased risk of DVT and PE exists in patients with multiple myeloma treated with lenalidomide combination therapy. It is not known if prophylactic anticoagulation or antiplatelet therapy may reduce the potential for venous thromboembolic events.Hematologic toxicity
Significant neutropenia and thrombocytopenia can develop in patients with deletion 5q myelodysplastic syndromes. Lenalidomide dose reduction/delay may be necessary. Patients may require use of blood product support and/or growth factors. Monitor CBC weekly for first 8 wk of therapy and at least monthly thereafter.Potential for human birth defects
Lenalidomide is an analog of thalidomide, a known human teratogen that causes severe, life-threatening human birth defects. If lenalidomide is taken during pregnancy, it may cause birth defects or death to the fetus. Advise women to avoid becoming pregnant while taking lenalidomide. Women of childbearing potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 wk after lenalidomide treatment. Lenalidomide is only available under a restricted distribution system.
Perform CBC, including WBC with differential, platelet count, Hgb, and Hct, weekly for first 8 wk of therapy and at least monthly thereafter in patients with MDS. In patients with multiple myeloma, perform CBC every 2 wk for the first 3 mo and monthly thereafter. Perform pregnancy tests in women of childbearing potential weekly for 4 wk after the start of treatment, then every 4 wk in women with regular menstrual cycles or every 2 wk in women with irregular menstrual cycles.
Category X .
Safety and efficacy not established.
Patients 65 y and older experience more frequent serious adverse reactions. Because elderly patients are more likely to have decreased renal function, take care in dose selection and monitor renal function.
Risk of adverse reactions may be increased. Take care with dose selection and monitor renal function. Dosage adjustment required.
Has been reported.
Stevens-Johnson syndrome and TEN have been reported. These events are serious and can be fatal.
Transient liver laboratory abnormalities (predominantly transaminases) have been reported. Interrupt treatment and restart once levels return to baseline.
Lenalidomide should not be started in sexually mature men unless patient meets the following conditions: understands the risks associated with the drug and is thought to be able to reliably carry out instructions; is capable of complying with the contraceptive measures that are appropriate for men, patient registration, and patient survey as described in the RevAssist program; has received oral and written warnings of potential risks of taking lenalidomide and exposing a fetus to the drug; has received oral and written warnings of the risk of possible contraception failure and that it is unknown whether lenalidomide is present in semen and of the need for barrier contraception (latex condoms even with successful vasectomy); acknowledges in writing the understanding of these warnings and of the need to use a latex condom during any sexual contact with women of childbearing potential; parent or legal guardian reads the educational materials and agrees to try to ensure compliance with above for patients between 12 and 18 y of age.
Tumor flare reaction
Has been reported during investigational use of lenalidomide for chronic lymphocytic leukemia and lymphoma, characterized by tender lymph node swelling, low-grade fever, pain, and rash.
Tumor lysis syndrome
Because lenalidomide has antineoplastic activity, complications of tumor lysis syndrome may occur. Fatal instances have been reported.
Lenalidomide should not be started in women of childbearing potential unless alternative therapies are inappropriate and patient meets the following conditions: understands the risks associated with the drug and is thought to be able to carry out instructions; is capable of complying with the contraceptive measures, pregnancy testing, patient registration, and patient survey as described in the RevAssist program; has received both oral and written warnings of potential risks of taking lenalidomide during pregnancy and of exposing a fetus to the drug; has received oral and written warnings of the risk of possible contraception failure and of the need to use 2 reliable forms of contraception simultaneously, unless continuous abstinence from heterosexual sexual contact is the chosen method. Sexually mature women who have not undergone a hysterectomy or who have not been menopausal for at least 24 consecutive months (have had menses at some time in the preceding 24 consecutive months) are considered to be of childbearing potential; acknowledges in writing the understanding of these warnings and of the need for using 2 reliable methods of contraception for 1 mo prior to starting lenalidomide therapy, during therapy, during dose interruption, and for 1 mo after stopping therapy; has had 2 negative pregnancy tests with a sensitivity of at least 50 milliunits/mL within 10 to 14 days and 24 h prior to beginning therapy. During therapy and during dose interruptions, pregnancy testing should occur weekly during first 4 wk of use, then every 4 wk in women with regular menstrual cycles, or every 2 wk in women with irregular menstrual cycles. Perform pregnancy testing if a patient misses a monthly menstrual cycle or if there is any abnormality in her pregnancy test or menstrual bleeding. Discontinue lenalidomide during this evaluation. Parent or legal guardian reads the educational materials and agrees to try to ensure compliance with above for patients between 12 and 18 y of age.
In studies, dose-limiting toxicity was hematological.
- Review guidelines and requirements for participation in the RevAssist program with patients or caregivers.
- Advise patients or caregivers to read the Medication Guide carefully before starting therapy and to read it each time the medication is refilled.
- Advise patients that regular blood tests will be required during treatment and that the dose of the medication may be adjusted or treatment interrupted based on results of blood tests and patient's general condition.
- Advise patients that medication will only be dispensed in a 28-day supply at one time and that he/she must comply with the RevAssist program requirements for monitoring, including pregnancy tests for women of childbearing potential, before the medication can be refilled.
- Instruct patients to take the prescribed dose with a glass of water once daily. Advise patients that medication can be taken without regard to meals but to take it with food if stomach upset occurs.
- Caution patients to swallow capsules whole and not to break, chew, or open the capsules.
- Instruct patients to immediately seek medical care if any of the following occur: arm or leg swelling; bleeding or unusual bruising; fever, sore throat, or other signs of infection; sudden chest pain; unexplained shortness of breath or difficulty breathing.
- Advise patients, families, or caregivers to notify their health care provider if rash, hives, persistent diarrhea, or excessive or unexplained tiredness develop.
- Advise patients that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
- Inform patients that they cannot give blood while taking lenalidomide and for 4 wk after stopping therapy.
- Advise men that they cannot donate sperm while taking lenalidomide and for 4 wk after stopping therapy.
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