Adult Dosing
Multiple myeloma
- Start dose: 25 mg PO once daily on Days 1-21 of repeated 28-day cycles
- Usual dose of dexamethasone: 40 mg PO daily on Days 1-4, 9-12, and 17-20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg PO daily on Days 1-4 q28 days
Myelodysplastic syndromes, deletion 5q type
Mantle cell lymphoma
- 25 mg PO once daily on Days 1-21 of repeated 28-day cycles
Note:
- Continue or modify dose based upon clinical and laboratory findings
- Avoid opening/crushing/chewing capsules
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
Renal Dose Adjustment (Based on CrCl)
- Multiple myeloma
- 30-60 mL/min: 10 mg PO q24 hr
- <30 mL/min (not requiring dialysis): 15 mg PO q48 hr
- <30 mL/min (requiring dialysis): 5 mg PO Daily; on dialysis days administer the dose following dialysis
- Myelodysplastic syndromes
- 30-60 mL/min: 5 mg PO q24 hr
- <30 mL/min (not requiring dialysis): 5 mg PO q48 hr
- <30 mL/min (requiring dialysis): 5 mg PO 3x/wk following each dialysis
- Mantle cell lymphoma
- CrCl 30-60 mL/min: 10 mg PO q24 hr
- CrCl <30 mL/min (not requiring dialysis): 15 mg PO q48hr
- <30 mL/min (requiring dialysis): 5 mg PO qd; on dialysis days, administer the dose following dialysis
Hepatic Dose Adjustment
- Hepatic impairment: Dose adjustments not defined
Dosage adjustment based on absolute neutrophil count (ANC) in Mylodysplastic syndrome
- Within 4 weeks of starting 10 mg daily and baseline ACN 1000/mcL or greater: stop lenalidomide for ANC less than 750/mcL; resume at 5 mg PO daily when ANC returns to 500/mcL or more
- Within 4 weeks of starting 10 mg daily and baseline ACN less then 1000/mcL: stop lenalidomide for ANC less than 500/mcL; resume at 5 mg PO daily when ANC returns to 500/mcL or more
- Neutropenia AFTER 4 weeks of starting 10 mg daily treatment
- Stop lenalidomide for ANC less then 500/mcL: for 7 days or more. or ANC less than 500.mcL associated with fever; resume at reduce dose of 5 mg PO daily when ANC returns to 500.mcL
- Neutopenia while taking 5 mg daily
- Stop Lenalidomide for ANC less then 500/mcL for 7 days or more, or ANC less then 500/mcL associated with fever; resume at 5 mg PO every OTHER day when ANC returns to 500/mcL
- Thrombocytopenia within 4 weeks of starting 10mg daily dose; stop lenalidomide for platelets less then 50,000/mcL; resume at 5 mg PO Daily once platelets return to 50,000/mcL or more.
- Thrombocytopenia within 4 weeks of staring 10 mg daily and baseline platelets 60,000/mcL or greater; stop lenalidomine if 50% drop of baseline; resume at 5 mg daily when platelets return to at least 50,000/mcL
- Thrombocytopenia within 4 weeks of starting 10 mg daily and baseline LESS than 60,000/mcL; stop lenlidomide if 50% drop of baseline; resume at 5 mg daily one platelets return to at least 30,000.mcL
- Thrombocytopenia AFTER 4 weeks of starting 10 mg daily: stop lenalidomide for platelets less than 30,000/mcL or less than 50,000/mcL associated with platelet transfussions; resume at 5 mg daily once platelets return to at least 30,000/mcL with out hemostatic failure
- Thrombocytopenia during treatment with 5 mg daily: stop lenalidomide for platelets less than 30,000/mcL or less than 50,000/mcL associated with platelet transfussions; resume at 5 mg every OTHER day once platelets return to at least 30,000/mcL with out hemostatic failure
Dosage adjustment based on platelet counts and absolute neutrophil counts (ANC) in Mantle cell lymphoma
- If platelet count falls to <50,000/mcL, then interrupt treatment and if returns to
50,000/mcL then resume at 5 mg/day less than previous dose; do not dose below 5 mg/day - If absolute neutrophil count falls to <1,000/mcL for at least 7 days or falls to <1,000/mcL with fever (38.5°C) or ANC <500/mcL then interrupt treatment and follow weekly CBC . If ANC returns to 1,000/mcL then start again at 5 mg/day less than previous dose; do not dose below 5 mg/day
- For Grade 3/4 toxicities : Interrupt treatment and resume at physicians discretion at next lower dose when toxicity has resolved to
Grade 2 - Continue or modify dose based upon clinical and laboratory findings
See Supplemental Patient Information
- This drug is available only under a RevAssist restricted distribution program for avoiding fetal exposure to lenalidomide. Only prescribers and pharmacists registered with the program can prescribe and dispense the product to patients having registered and meeting all the conditions of the RevAssist program [US Black Box Warning]
- Use of lenalidomide, a thalidomide analogue is associated with birth defects; birth defects including death have occurred to a developing baby on using this drug during pregnancy. Advise women of childbearing potential to use two reliable methods of contraception for prevention of pregnancy including during therapy interruptions and for at least 4 wks after completion of therapy; advise them to continuously abstain from heterosexual sex during and for 4wks after therapy with this drug [US Black Box Warning]
- Exclude pregnancy before initiation of therapy by obtaining 2 negative pregnancy tests. Perform first test within 10-14 days and the second test within 24 hrs prior to prescribing lenalidomide. Advise women of childbearing potential to use two reliable methods of contraception for prevention of pregnancy; advise them to continuously abstain from heterosexual sex during and for 4 wks after therapy with this drug [US Black Box Warning]
- Advise males to use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy
- Perform pregnancy test for females of childbearing potential qwk during the first 4 wks of use, then repeat q4 wks in females with regular menstrual cycles. If irregular menstrual cycles perform the pregnancy tests q2 wk. Perform pregnancy testing and counseling if a patient misses her period or if there is any abnormality in her pregnancy test or in her menstrual bleeding. Discontinue therapy during this evaluation. Verify pregnancy test prior to dispensing to any prescription. Immediately discontinue therapy on occurrence of pregnancy
- Report any suspected fetal exposure to the FDA. Refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling
- Use therapy in females of childbearing potential and males only if they comply with mandatory contraceptive measures, pregnancy testing (females), patient registration, patient survey and all other conditions meeting as per the RevAssist Program
- Provide females of childbearing potential and males oral and written warnings of the potential risks for taking this drug and exposing this drug to a fetus
- Significant neutropenia and thrombocytopenia have occurred in association with use of this drug. Modification of dosing regimen with either delaying dosing or dose reduction was essential in 80% of patients with del 5q myelodysplastic syndromes in a major study. 34% of patients were in need for delaying second dose or dose reduction. Monitor CBC weekly for the first 8wks and monthly thereafter in patients with del 5q myelodysplastic syndromes. Dose interruption and/or dose reduction may be required in some patients.
- Use of blood product and/or growth factors may be needed in some patients.
- Grade 3 and 4 hematologic toxicities have occurred more frequent in patients treated with combination of lenalidomide and dexamethasone than in patients treated with dexamethasone alone [US Black Box Warning]
- Significant increase in risk of deep vein thrombosis and pulmonary embolism have occurred in patients with multiple myeloma receiving lenalidomide with dexamethasone and in patients with myelodysplastic syndromes treated with lenalidomide monotherapy. Monitor patients for signs and symptoms of thromboembolism and also advise patients for observing signs and symptoms of thromboembolism. Instruct patients to seek medical care on developing symptoms such as shortness of breath, chest pain, or swelling of arm/leg. Unknown whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with lenalidomide decreases the potential for venous thromboembolic events. Take utmost care for deciding prophylactic measures after assessing individual patient’s underlying risk factors [US Black Box Warning]
- Fatal angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have occurred. Avoid therapy in patients having prior history of Grade 4 rash associated with thalidomide
- Consider interruption or discontinuation of therapy for Grade 2-3 skin rash. Discontinue therapy on occurrence of angioedema, Grade 4 rash, exfoliative or bullous rash or on suspection of SJS or TEN. Avoid restarting of therapy following resolving of these reactions
- Fatal instances of tumor lysis syndrome have occurred. Patients with high tumor burden prior to treatment are at higher risk
- During investigational use of lenalidomide for CLL and lymphoma tumor flare reaction has occurred. Discourage treatment of CLL or lymphoma with lenalidomide outside of a well-monitored clinical trial
- Patient receiving lenalidomide are at higher risk of second primary malignancies, especially acute myelogenous leukemia (AML) and Hodgkin lymphoma. Monitor patients for the development of second malignancies, taking into account potential benefit of lenalidomide and the risk of second primary malignancies when considering treatment with lenalidomide
- Avoid blood donation during treatment and for 1 month following discontinuation
Cautions: Use cautiously in
- Renal impairment
- Risk of thrombosis
Supplemental Patient Information
- Counsel patients about the potential risk of teratogenicity associated with this drug
- Inform patients about the importance of monthly pregnancy tests and the need to use two different forms of contraception including at least one highly effective form simultaneously
Pregnancy Category:X
Breastfeeding: Unknown whether this drug is excreted in human milk. Potential for adverse reactions in nursing infants from lenalidomide exists. According to manufacturer's data a decision is essential for discontinuing nursing or discontinuing the drug taking into account the importance of the drug to the mother.
