Lenalidomide

Lenalidomide is a prescription medicine used to treat the symptoms of myelodysplastic syndromes (MDS), multiple myeloma (MM), mantle cell lymphoma (MCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL).

• Lenalidomide is available under the following different brand names: Revlimid

Adult dosage

Capsule

• 2.5mg
• 5mg
• 10mg
• 15mg
• 25mg

Myelodysplastic Syndromes

Adult dosage

• 10 mg orally once daily; treatment is modified based upon clinical and laboratory findings
• Continue treatment until disease progression or unacceptable toxicity

Multiple Myeloma

Adult dosage

Treatment

• 25 mg orally once daily on Days 1-21 of repeated 28-day cycles (use with dexamethasone)
• Dexamethasone schedule
  • 40 mg orally once daily on Days 1-4, 9-12, and 17-20 of each 28-day cycle for the first 4 cycles, THEN
  • 40 mg orally once daily on Days 1-4 every 28 days
  • Age above 75 years: 20 mg orally once daily on Days 1, 8, 15, and 22 of each 28-day cycle

Maintenance

• Starting dose: 10 mg orally once daily continuously (i.e., Day 1-28 of repeated 28-day cycles) until disease progression or unacceptable toxicity
• After 3 cycles: May increase dose to 15 mg orally once daily if tolerated

Mantle Cell Lymphoma

Adult dosage

• 25 mg orally once daily on Days 1-21 of repeated 28-day cycles; treatment is modified based on clinical or laboratory findings
• Continue until disease progression or unacceptable toxicity

Follicular Lymphoma or Marginal Zone Lymphoma

Adult dosage

• Rituximab 375mg/m² IV every Week in Cycle 1 (Days 1, 8, 15, and 22) on Day 1 of every 28-day cycle from Cycles 2-5  
• Lenalidomide 20 mg orally once daily on Days 1-21 every 28 days up to 12 cycles

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Lenalidomide include:

• fever,
• cough,
• tiredness,
• itching,
• rash,
• swelling,
• nausea,
• diarrhea, and
• constipation.

Serious side effects of Lenalidomide include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• severe skin reaction,
• sore throat,
• burning in the eyes,
• skin pain,
• red or purple skin rash that spreads and causes blistering and peeling,
• sudden numbness or weakness,
• severe headache,
• problems with speech or vision,
• shortness of breath,
• swelling or redness in the arm or leg,
• chest pain or pressure,
• pain spreading to jaw or shoulder,
• sweating,
• chills,
• swollen gums,
• mouth sores,
• skin sores,
• easy bruising,
• unusual bleeding,
• swollen glands,
• low fever,
• rash,
• lower back pain,
• blood in urine,
• little or no urination,
• numbness or tingly feeling around mouth,
• confusion, and
• fainting.

Rare side effects of Lenalidomide include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Lenalidomide has severe interactions with the following drug:
  • anakinra
• Lenalidomide has serious interactions with the following drugs:
  • deferiprone
  • palifermin
  • ropeginterferon alfa 2b
  • selinexor
  • vedolizumab
• Lenalidomide has moderate interactions with the following drugs:
  • acalabrutinib
  • cholera vaccine
  • denosumab
  • dichlorphenamide
  • fingolimod
  • hydroxyurea
  • ponesimod
  • siponimod
  • sipuleucel-T
  • trastuzumab
  • trastuzumab deruxtecan
  • zidovudine
  • Lenalidomide has minor interactions with the following drugs: 
  • food
  • tocilizumab

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Pregnancy; sexually active women of childbearing potential not using 2 forms of contraception
• Demonstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Lenalidomide?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lenalidomide?”

Cautions

• The risk of hematologic toxicity; can cause significant neutropenia and thrombocytopenia (see Dosage Modifications)
• Use caution in renal impairment
• Increases risk of mortality in patients with CLL with monotherapy; therapy not indicated and not recommended in CLL outside of controlled clinical trials
• Fatal instances of tumor lysis syndrome reported
• Patients must not donate blood during treatment and for 4 weeks following discontinuation of the drug because the blood might be given to pregnant female patients whose fetuses must not be exposed to drug
• Tumor flare reaction (TFR) has occurred during investigational use for CLL and lymphoma, and is characterized by tender lymph node swelling, low-grade fever, pain, and rash; tumor flare may mimic the progression of disease; may continue treatment if grade 1 or 2 TFR (treat with corticosteroids, NSAIDs, and/or narcotic analgesics), hold treatment for grade 3 or 4 TFR until resolves to less than or equal to Grade 1
• Hepatic failure, including fatal cases, has occurred when administered in combination with dexamethasone; the mechanism of drug-induced hepatotoxicity is unknown; pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors; monitor liver enzymes periodically; stop therapy upon elevation of liver enzymes; after return to baseline values, treatment at a lower dose may be considered
• Patients treated with lenalidomide (with melphalan and stem cell transplantation) had a higher incidence of second primary malignancies, particularly acute myelogenous leukemia (AML) and Hodgkin lymphoma, compared to patients in the control arms who received similar therapy but did not receive lenalidomide
• Monitor patients for the development of second primary malignancies; take into account both potential benefit of therapy and risk of second primary malignancies when considering therapy
• Impaired stem cell mobilization reported; refer patients who are auto-HSCT candidates to a transplant center early in treatment to optimize the timing of the stem cell collection; patients who received more than 4 cycles of treatment or for whom inadequate numbers of CD 34+ cells have been collected with G-CSF alone, G-CSF with cyclophosphamide or the combination of GCSF with a CXCR4 inhibitor may be considered
• Both hypothyroidism and hyperthyroidism reported: measure thyroid function before initiating and during therapy
• Tumor lysis syndrome reported with therapy; monitor patients at risk closely; take appropriate preventive approaches
• Increased mortality was observed in 2 randomized clinical trials in patients with multiple myeloma when pembrolizumab was added to a thalidomide analog and dexamethasone; treatment with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analog plus dexamethasone is not recommended outside of controlled clinical trials
• Venous and arterial thromboembolism
  • Increased risk of DVT, PE, MI, and stroke associated with therapy
  • Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g. hyperlipidemia, hypertension, smoking)
  • Thromboprophylaxis is recommended; the regimen of thromboprophylaxis should be based on an assessment of the patient’s underlying risks; instruct patients to report immediately any signs and symptoms suggestive of thrombotic events; ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision in patients receiving therapy
• Hematologic toxicity
  • Monitor patients with neutropenia for signs of infection; advise patients to observe for bleeding or bruising, especially with the use of concomitant medication that may increase risk of bleeding; patients receiving therapy should have their complete blood counts assessed periodically
  • Monitor complete blood counts (CBC) in patients receiving therapy in combination with dexamethasone or as maintenance therapy 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
  • Monitor CBC, in patients taking therapy, for MCL weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly thereafter
  • Monitor complete blood counts (CBC) in patients receiving therapy for FL or MZL weekly for the first 3 weeks of Cycle 1 (28 days), every 2 weeks during Cycles 24, and then monthly thereafter
• Angioedema and serious dermatologic reactions
  • Angioedema and severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) reported; DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis; these events can be fatal
  • Patients with prior history of Grade 4 rash associated with thalidomide treatment should not receive lenalidomide
  • Consider interrupting or discontinuing for Grade 2-3 skin rash
  • Discontinue for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected and should not be resumed following discontinuation for these reaction.
• Drug interactions overview
• Digoxin
  • Coadministration of lenalidomide (multiple doses of 10 mg/day) with digoxin may increase plasma levels of digoxin; monitor digoxin plasma levels based on clinical judgment and standard practices
• Therapies that increase the risk of thrombosis
  • Use erythropoietic agents or other agents that may increase the risk of thrombosis, such as estrogen containing therapies, with caution after making a benefit-risk assessment in patients receiving Lenalidomide
• Warfarin
  • Coadministration of lenalidomide with a single dose of warfarin did not affect the pharmacokinetics of lenalidomide or R- and S-warfarin
  • Expected changes in PT and INR were observed after warfarin administration
  • Unknown whether an interaction between dexamethasone and warfarin
  • Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin
• Pregnancy and Lactation
  • Contraindicated during pregnancy (see Contraindications and Black Box Warnings)
  • Based on the mechanism of action and findings from animal studies, lenalidomide can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy
  • Thalidomide analog; thalidomide is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), bone hypoplastic, absence of bones, external ear abnormalities (including anotia, microtia, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects
  • Mortality at or shortly after birth has been reported in ~40% of infants
• Contraception
• Females
  • Females of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously: one highly effective form of contraception (eg, tubal ligation, IUD, hormonal [birth control pills, injections, hormonal patches, vaginal rings, or implants]), or partner’s vasectomy, and 1 additional effective contraceptive method (eg, male latex or synthetic condom, diaphragm, or cervical cap)
  • Contraception must begin 4 weeks before initiating treatment, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of therapy
  • Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy
  • Females of reproductive potential should be referred to a qualified provider of contraceptive methods if needed
• Males 
  • Present in the semen of males; therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide and for up to 4 weeks after discontinuing, even if they have undergone a successful vasectomy
  • Male patients taking lenalidomide must not donate sperm
• Pregnancy registry
  • There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to lenalidomide during pregnancy as well as female partners of male patients who are exposed
  • This registry is also used to understand the root cause for the pregnancy
  • Report any suspected fetal exposure to lenalidomide to the FDA via the MedWatch program at 1-800-FDA-1088 and also to the manufacturer at 1-888-423-5436
• Lactation
  • Unknown if distributed into human breast milk
  • Because of the potential for adverse reactions in breastfed infants from lenalidomide, advise women not to breastfeed during treatment