Lenalidomide

Class: Immunomodulatory Agents
Chemical Name: 3-(4-Amino-1-3-dihydro-1-oxo-2H-isoindol-2yl)-2,6-piperidinedione
Molecular Formula: C13H13N3O3
CAS Number: 191732-72-6
Brands: Revlimid

Warning(s)

  • Teratogenic Effects
  • Potential risk of teratogenicity and fetotoxicity due to structural similarity to thalidomide, a known human teratogen that can cause severe, life-threatening birth defects if administered during pregnancy.1 7 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Teratogenicity Precautions
  • Contraindicated in pregnant women; use in women of childbearing potential only when alternative treatments are not available and adequate precautions taken to prevent fetal exposure.1 (See Contraindications and also Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Pregnancy must be excluded with 2 confirmed negative pregnancy tests (sensitivity to detect human serum chorionic gonadotropin [HCG] concentrations of ≥50 million IU/mL); one test within 10–14 days and another ≤24 hours prior to treatment initiation.1 j Repeat pregnancy tests throughout therapy (i.e., once weekly during first month, then monthly or every 2 weeks in women with regular or irregular menstrual cycles, respectively).1 7 j

  • Pregnancy must be prevented (even in females with a history of infertility) by simultaneous use of 2 forms of reliable contraception for ≥4 weeks prior to, throughout, and for 4 weeks after completion of therapy.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Mandatory contraception not required for females who have undergone hysterectomy or bilateral oophorectomy, are postmenopausal and have had no menses for ≥24 consecutive months, or practice continuous abstinence from heterosexual contact.1

  • Sexually mature males (including successfully vasectomized men) must completely avoid unprotected sexual contact with women of childbearing potential (i.e., use latex condom throughout and for ≥4 weeks after lenalidomide therapy) because it is unknown if drug distributes into semen.1 7

  • Provide pregnancy tests and counseling if a patient misses her period or has abnormalities in menstrual bleeding.1

  • If pregnancy occurs, immediately discontinue treatment.1 Refer patient to obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling.1 Report any suspected fetal exposure to FDA MedWatch Program at 1-800-FDA-1088 and to manufacturer at 1-888-423-5436.1

  • Restricted Distribution Program
  • Available only through restricted distribution program, the RevAssist program, designed because of potential teratogenicity and to help ensure that fetal exposure does not occur.1 (See Restricted Distribution Program under Dosage and Administration.)

  • Limits access to lenalidomide to prescribing clinicians, pharmacies, and patients who are registered in program and mandates compliance with registration, education, and safety requirements.1 7 j

  • Registered prescribing clinicians must understand risks of teratogenicity if used during pregnancy and must not provide a prescription until a documented negative pregnancy test available.1

  • Patient or parent/legal guardian (for minors 12–18 years of age) must be capable of understanding and complying with patient registration, education, patient survey, and safety requirements, including mandatory contraceptive measures and pregnancy testing.1 7

  • Provide oral and written warnings of risk of possible contraceptive failure, hazards of using drug during pregnancy, exposing fetus to drug, and possibility of drug in semen.1 7

  • Patient or parent/legal guardian must provide written acknowledgment of understanding of these warnings and need for mandatory contraceptive measures.1 7

  • Hematologic Toxicity
  • Risk of severe thrombocytopenia and neutropenia.1 7 (See Hematologic Effects under Cautions.)

  • Grade 3 or 4 neutropenia and/or thrombocytopenia reported in 80% of patients with myelodysplastic syndromes (MDS) with deletion 5q abnormality.1 Dosage delay or reduction required in 80% of such patients; a second dosage delay or reduction required in 34% of patients.1

  • Monitor CBCs weekly for the first 8 weeks of therapy for MDS and at least monthly thereafter.1 Dosage interruption and/or reduction and supportive therapy (e.g., blood products) and/or hematopoietic agents (colony-stimulating factors) may be required.1 (See Dosage Modification for Toxicity in Patients with MDS under Dosage and Administration.)

  • Thromboembolic Effects
  • Increased risk of venous thromboembolism (e.g., DVT, PE) in patients with multiple myeloma when used in combination with dexamethasone.1 7 20 c h

  • Monitor for signs and symptoms of thromboembolism.1 7

  • Base decisions regarding thromboprophylaxis on careful assessment of patient’s risk factors.20 40 41 42 (See Thromboembolic Events under Cautions.)

REMS:

FDA approved a REMS for lenalidomide to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of lenalidomide and consists of the following: elements to assure safe use and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Biologic response modifier; thalidomide analog with immunomodulatory, antineoplastic, and antiangiogenic activity.1 a b c d e 30

Uses for Lenalidomide

Myelodysplastic Syndrome (MDS)

Treatment of RBC transfusion-dependent anemia associated with low- or intermediate-1-risk MDS in patients with a cytogenetic deletion abnormality involving the long arm of chromosome 5 (deletion 5q abnormality), with or without additional cytogenetic abnormalities1 3 5 7 30 (designated an orphan drug by FDA for this use).6

Slideshow: Flashback: FDA Drug Approvals 2013

Use of lenalidomide for the treatment of transfusion-dependent low-risk or intermediate-1-risk MDS without the deletion 5q chromosomal abnormality is a reasonable choice (accepted, with possible conditions).35

Multiple Myeloma

Treatment of multiple myeloma (in combination with dexamethasone) in patients who have received at least one prior therapy1 7 (designated an orphan drug by FDA for this use).6

Combination therapy with dexamethasone substantially more effective than dexamethasone monotherapy in achieving overall, complete, and partial response in patients who have received at least one prior therapy.1

Lenalidomide Dosage and Administration

General

  • Adjust dosage carefully according to individual response and laboratory parameters (e.g., blood cell counts).1 7

  • Carefully monitor CBCs (including differential and platelets) during therapy.1 (See Hematologic Effects under Cautions.)

Administration

Restricted Distribution Program

Distribution of lenalidomide is restricted because it is an analog of thalidomide (a known teratogen that can cause severe birth defects).1 (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Must be obtained through a restricted distribution program (RevAssist) to ensure that fetal exposure to lenalidomide does not occur.1 c j The program requires registration of clinicians, pharmacies, and patients; all must agree to accept specific responsibilities (e.g., mandatory contraceptive measures, pregnancy testing) designed to minimize pregnancy exposures in order to prescribe, dispense, or use lenalidomide.1 7 j

RevAssist program ensures appropriately timed and properly documented pregnancy testing and counseling of patients before, during, and following lenalidomide therapy.1

Prior to initiation of therapy, females must certify that they are not pregnant or not of childbearing potential (i.e., have undergone hysterectomy or bilateral oophorectomy, postmenopausal [no menses for ≥24 consecutive months]).1

Pharmacists registered with the restricted distribution program must offer counseling, provide educational materials (e.g., patient information guide), and confirm negative pregnancy test results (in women of childbearing potential) each time drug is dispensed.1 c j

To facilitate pregnancy testing and counseling in accordance with RevAssist program, prescribe and dispense ≤28-day supply of drug.1 7 c j Patients and prescribers must participate in monthly telephone surveys to receive authorization for each prescription written.1 c j

For additional details on program requirements, contact Celgene at 888-423-5436 or see RevAssist website at .1 7 j

Oral Administration

Administer orally with water once daily.1 7

Swallow capsules whole; do not break, chew, or open capsules.1 7

Administer as a single 25-mg capsule for treatment of multiple myeloma.1 Effects of substituting lower-strength capsules to achieve a 25-mg dose not known.1

If a dose is missed, take as soon as remembered; if a dose is missed for an entire day, skip dose and resume regular dosing schedule the following day.7 Do not double a dose.7

Manufacturer makes no specific recommendations regarding administration with meals; food may decrease peak plasma concentrations.1 (See Food under Pharmacokinetics.)

Dosage

Adults

Myelodysplastic Syndrome
MDS with Deletion 5q Abnormality
Oral

Initially, 10 mg once daily.1 Continue or adjust initial dosage based on clinical response and laboratory parameters (e.g., blood cell counts).1 7

If thrombocytopenia and/or neutropenia occur, reduce dosage or interrupt therapy based on degree of myelosuppression.1 (See Dosage Modification for Toxicity in Patients with MDS under Dosage and Administration.)

MDS without Deletion 5q Abnormality
Oral

Dosage of 10 mg once daily has been used.30

Dosage Modification for Toxicity in Patients with MDS
Oral
Table 1. Dosage Adjustment for Thrombocytopenia Occurring ≤4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage

Platelet Count (per mm3)

Dosage Adjustment

10 mg

Baseline count ≥100,000 and then decreases to <50,000

Discontinue therapy; when count returns to ≥50,000/mm3, resume therapy at 5 mg daily1

10 mg

Baseline count <100,000 and then decreases to 50% of baseline

Discontinue therapy; when count returns to ≥50,000/mm3 (for baseline ≥60,000/mm3) or ≥30,000/mm3 (for baseline <60,000/mm3), resume therapy at 5 mg daily1

5 mg

<30,000 or <50,000 (with platelet transfusions)

Discontinue therapy; when count returns to ≥30,000/mm3 (without hemostatic failure), resume therapy at 5 mg every other day1

Table 2. Dosage Adjustment for Thrombocytopenia Occurring >4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage

Platelet Count (per mm3)

Dosage Adjustment

10 mg

<30,000 or <50,000 (with platelet transfusions)

Discontinue therapy; when count returns to ≥30,000/mm3 (without hemostatic failure), resume therapy at 5 mg daily1

5 mg

<30,000 or <50,000 (with platelet transfusions)

Discontinue therapy; when count returns to ≥30,000/mm3 (without hemostatic failure), resume therapy at 5 mg every other day1

Table 3. Dosage Adjustment for Neutropenia Occurring ≤4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage

ANC (per mm3)

Dosage Adjustment

10 mg

Baseline ≥1000 and then decreases to <750

Discontinue therapy; when ANC returns to ≥1000/mm3, resume therapy at 5 mg daily1

10 mg

Baseline ANC <1000 and then decreases to <500

Discontinue therapy; when ANC returns to ≥500/mm3, resume therapy at 5 mg daily1

5 mg

If ANC decreases to <500 for ≥7 days or decreases to <500 associated with fever (≥38.5°C)

Discontinue therapy; when ANC returns to ≥500/mm3, resume therapy at 5 mg every other day1

Table 4. Dosage Adjustment for Neutropenia Occurring >4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage

ANC (per mm3)

Dosage Adjustment

10 mg

If ANC decreases to <500 for ≥7 days or decreases to <500 associated with fever (≥38.5°C)

Discontinue therapy; when ANC returns to ≥500/mm3, resume therapy at 5 mg daily1

5 mg

If ANC decreases to <500 for ≥7 days or decreases to <500 associated with fever (≥38.5°C)

Discontinue therapy; when ANC returns to ≥500/mm3, resume therapy at 5 mg every other day1

Multiple Myeloma
Oral

Initially, 25 mg once daily given on days 1–21 of each 28-day cycle.1 d e Administer with oral dexamethasone 40 mg daily on days 1–4, 9–12, and 17–20 of each 28-day cycle for the first 4 cycles of therapy, then reduce to 40 mg daily on days 1–4 of subsequent cycles.1 d e

Continue or adjust initial dosage based on clinical response and laboratory parameters (e.g., blood cell counts).1 7 (See Dosage Modification for Toxicity in Patients with Multiple Myeloma Under Dosage and Administration.)

Dosage Modification for Toxicity in Patients with Multiple Myeloma
Hematologic Toxicity.
Oral

Continue at reduced dosage for remainder (up to 21 days) of treatment cycle.

Table 5. Dosage Adjustment for Thrombocytopenia During Therapy

Platelet Count (per mm3)

Dosage Adjustment

<30,000

Discontinue therapy and monitor CBCs weekly;1 when count returns to ≥30,000/mm3, reduce dosage to 15 mg daily

For each subsequent decrease to <30,000

Discontinue therapy;1 when count returns to ≥30,000, resume at a dosage 5 mg less than previous dose; do not administer <5 mg daily

Continue at reduced dosage for remainder (up to 21 days) of a 28-day treatment cycle.

Table 6. Dosage Adjustment for Neutropenia During Therapy

ANC (per mm3)

Dosage Adjustment

<1000

Discontinue therapy, add a granulocyte colony-stimulating factor (G-CSF), and monitor CBCs weekly1

≥1000 (following discontinuation of therapy ) and no other toxicity present

Resume at 25 mg daily1

≥1000 (following discontinuation of therapy) and other toxicity present

Reduce dosage to 15 mg daily1

For each subsequent decrease to <1000

Discontinue therapy; when count returns to ≥1000/mm3, resume at a dosage 5 mg less than previous dose; do not administer <5 mg daily1

Other Grade 3/4 Toxicities.

If patient experiences other grade 3 or 4 nonhematologic toxicities, interrupt therapy and resume at next lower dosage level when toxicity resolves or decreases to ≤grade 2 (i.e., reduce to 15 mg; if necessary, further reduce dosage 5 mg less than previous dose [not <5 mg daily given on days 1–21 of each 28-day cycle]).1 8

Prescribing Limits

Adults

Multiple Myeloma
Oral

Minimum 5 mg daily given on days 1–21 of each 28-day cycle.1

Special Populations

Renal Impairment

Myelodysplastic Syndrome
Oral
Dosage for Treatment of MDS in Adults with Renal Impairment8f

Clcr (mL/min)

Dosage

≥50

10 mg once daily

30–49

5 mg once daily

<30 (not requiring dialysis)

5 mg every 48 hours

End stage renal disease (requiring dialysis)

5 mg 3 times a week following each dialysis

Multiple Myeloma
Oral

Dosage may be increased to 15 mg once daily after 2 cycles in patients who have not responded to therapy.

Based on dosing for 21 days of a 28-day cycle.

Dosage for Multiple Myeloma in Adults with Renal Impairment8f

Clcr (mL/min)

Dosage

≥50

25 mg once daily

30–49

10 mg once daily,

<30 (not requiring dialysis)

15 mg every 48 hours

End stage renal disease (requiring dialysis)

15 mg 3 times a week following each dialysis

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function; reduced dosages may be required.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Lenalidomide

Contraindications

  • Pregnancy.1 7 (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Females of childbearing potential, unless they comply with all special conditions required by manufacturer and RevAssist program.1 (See Boxed Warning and see Restricted Distribution Program under Dosage and Administration.)

  • Known hypersensitivity to lenalidomide or any ingredient in the formulation.1 7

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.1 7 Teratogenic effects of lenalidomide not fully established, but considered a potential teratogen due to structural similarity to thalidomide, a known human teratogen associated with severe birth defects and fetal death.1 7 g (See Boxed Warning.)

Contraindicated in female patients who are or may become pregnant unless alternative therapies not available and adequate precautions taken to avoid pregnancy.1

Women of childbearing potential must use 2 forms of effective contraception ≥4 weeks prior to, throughout, and for 4 weeks following completion of therapy.1 7 Use a highly effective birth control method (e.g., intrauterine device [IUD]; oral, injectable, or implanted hormonal contraceptive; tubal ligation; vasectomized partner) and an effective barrier method (e.g., latex condom, diaphragm, cervical cap).1 If either IUD or hormonal contraceptive use contraindicated, may use another highly effective method or 2 simultaneous effective barrier methods.1

If clinician not available, information about emergency contraception (including information regarding clinicians who provide emergency contraceptive services) can be obtained by calling 1-888-668-2528.1

Not known whether lenalidomide is present in semen; sexually mature males (including those who have undergone successful vasectomy) receiving lenalidomide must use a latex condom each time they have sexual contact with a woman of childbearing potential during therapy and for 4 weeks following completion of therapy.1 7

Hematologic Effects

Risk of severe (grade 3 or 4) neutropenia and/or thrombocytopenia.1 3 7 a 30

Grade 3/4 hematologic toxicities reported in about 80% of patients with MDS associated with deletion 5q abnormality.1 Generally occurs during initial weeks (approximately 6 weeks for neutropenia and 4 weeks for thrombocytopenia) of treatment and reverses with dosage reduction or discontinuance.1 3 5

Higher frequency of grade 3/4 hematologic toxicities reported in patients with multiple myeloma receiving combination therapy with dexamethasone compared with those receiving dexamethasone alone.1

Carefully monitor hematologic status during therapy.1 Obtain baseline CBCs.j In patients with MDS, perform weekly CBCs during first 8 weeks of therapy, and at least monthly thereafter.1 In patients with multiple myeloma, perform CBCs every 2 weeks for the first 12 weeks of therapy, and at least monthly thereafter.1

If hematologic toxicity occurs, interrupt therapy and/or reduce dosage according to degree of myelosuppression.1 (See Dosage Modification for Toxicity in Patients with MDS and also Dosage Modification for Toxicity in Patients with Multiple Myeloma under Dosage and Administration.) Initiate supportive therapy with blood product transfusions or growth factors (e.g., G-CSF) if indicated.1 5

Thromboembolic Events

Risk of venous thromboembolism (e.g., DVT, PE) in patients with multiple myeloma, especially when used in combination with dexamethasone.1 7 20 c h Venous thromboembolism also reported in patients with MDS or mantle cell lymphoma receiving lenalidomide monotherapy.40

Monitor for signs and symptoms of thromboembolism (e.g., shortness of breath, chest pain, arm or leg swelling).1

Carefully assess patients for risk factors for thromboembolism; base decisions regarding use of thromboprophylaxis and appropriate thromboprophylaxis regimens (e.g., aspirin, anticoagulant) on patient's risk.1 20 41 42 c d h

International Myeloma Working Group (IMWG) recommends aspirin for lenalidomide-treated multiple myeloma patients with ≤1 individual and/or myeloma-related risk factor and a low molecular weight heparin (LMWH) for those with ≥2 such risk factors.20 IMWG also recommends that thromboprophylaxis with an LMWH be considered in patients receiving lenalidomide with high-dose dexamethasone, doxorubicin, or multiple antineoplastic agents, independent of additional risk factors.20 IMWG states full-dose warfarin (INR 2–3) is an alternative to LMWHs, but clinical experience is limited.20

ASCO recommends pharmacologic thromboprophylaxis for multiple myeloma patients receiving lenalidomide with dexamethasone or antineoplastic agents.42 Those at lower risk for thromboembolism may receive aspirin or an LMWH; those at higher risk should receive an LMWH.42

Specific Populations

Pregnancy

Category X.1 (See Contraindications and also Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether lenalidomide is distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 7

Geriatric Use

No substantial differences in efficacy relative to younger adults; however, increased incidence of serious adverse effects reported in patients >65 years of age compared with younger patients.1 8

Principally eliminated by kidneys.1 Assess renal function and select dosage carefully due to greater frequency of decreased renal function in geriatric patients.1 (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Substantially eliminated by kidneys; possible increased toxicity in patients with renal impairment.1

Monitor renal function; adjust dosage if necessary based on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

MDS: Thrombocytopenia,1 3 5 b 30 neutropenia,1 3 5 b c 30 diarrhea,1 3 7 30 pruritus,1 3 7 30 rash,1 7 30 fatigue,1 3 7 30 constipation,1 30 nausea,1 30 nasopharyngitis,1 arthralgia,1 back pain,1 fever,1 peripheral edema,1 30 cough,1 dizziness,1 headache,1 muscle cramps,1 dyspnea,1 pharyngitis,1 asthenia,1 epistaxis,1 upper respiratory tract infection,1 dry skin,1 abdominal pain,1 anemia,1 pneumonia,1 hypokalemia,1 limb pain,1 urinary tract infection,1 anorexia,1 edema,1 3 insomnia,1 vomiting.1

Multiple myeloma: Constipation,1 d fatigue,1 d insomnia,1 muscle cramps,1 diarrhea,1 neutropenia,1 anemia,1 asthenia,1 fever,1 nausea,1 headache,1 peripheral edema,1 dizziness,1 dyspnea,1 tremor,1 weight loss,1 thrombocytopenia,1 rash,1 d back pain,1 hyperglycemia,1 muscle weakness,1 blurred vision,1 cough,1 dyspepsia,1 anorexia,1 upper respiratory tract infection,1 dysgeusia,1 paresthesia,1 hypokalemia,1 pneumonia,1 arthralgia,1 vomiting.1

Interactions for Lenalidomide

Not metabolized by CYP isoenzymes.1 Does not inhibit or induce CYP isoenzymes.1

Specific Drugs

Drug

Interaction

Comments

Digoxin

Increased peak plasma digoxin concentrations1

Monitor plasma digoxin concentrations1

Warfarin

No pharmacokinetic interaction observed with single dose of warfarin1

Lenalidomide Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration.1 f

In healthy patients, peak plasma concentrations attained within approximately 0.625–1.5 hours following oral administration.1 c f

In patients with multiple myeloma, peak plasma concentrations attained within 0.5–4 hours following oral administration.1 AUC is 57% higher than in healthy male volunteers.1

Food

Food decreases peak plasma concentrations by 36%,1 but does not alter extent of absorption.1 f

Special Populations

In multiple myeloma patients with mild renal impairment, AUC increased by 56% compared with those with normal renal function.1

Distribution

Extent

Not known whether distributed into human milk.1

Not known whether crosses placenta in humans; embryocidal effects observed in rabbits.1 l

Not known whether distributed into semen.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Plasma Protein Binding

Approximately 30–40%.1 f

Elimination

Metabolism

Metabolic fate not known.1 In vitro studies indicate that lenalidomide does not undergo metabolism via CYP isoenzymes.1

Elimination Route

Primarily excreted in urine (67%) as unchanged drug via glomerular filtration and tubular secretion.1 f

Partially (about 30%) removed by hemodialysis.f

Half-life

Approximately 3–4 hours.1 c f

No evidence of drug accumulation with multiple dosing.1 f

Special Populations

In patients with renal impairment (Clcr <50 mL/minute), clearance reduced, systemic exposure increased, and half-life prolonged.f

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1 7

Actions

  • A thalidomide analog; similar in structure, but functionally distinct.b c h Exhibits more potent immunomodulating effectsa c d and lack of CNS effects compared with thalidomide.3 b Insufficient information regarding teratogenic potential of lenalidomide.1

  • Exact mechanism of action not fully elucidated.1 a b Affects a broad range of ligand-induced responses, including angiogenesis, inflammation, immune response, and cell adhesion.1 3 c

  • Antiangiogenic effects include inhibition of vascular endothelial growth factor (VEGF), an angiogenic cytokine secreted by bone marrow stromal cells and myeloma cells.c

  • Enhances cell-mediated immunity by inhibiting secretion of proinflammatory cytokines (e.g., tumor necrosis factor [TNF; TNF-α]), and stimulating interleukin-2, interferon gamma, cytolytic T-cell and natural killer (NK) cell responses.1 3 a c 30

  • Interferes with growth signaling between myeloma cells and bone marrow stromal cells by modulating expression of cell surface adhesion molecules.c

  • Exhibits direct antitumor effects by inducing cell cycle arrest and apoptosis in certain myeloma cell lines.1 8 a b c

  • Improves erythropoiesis in patients with low- or intermediate-1-risk MDS associated with a deletion 5q abnormality alone or with additional chromosomal abnormalities.1 30 May have direct antiproliferative activity against deletion 5q cell lines.3 5 b

Advice to Patients

  • Importance of comprehensive counseling (i.e., orally and in writing) on benefits and risks (i.e., severe, potentially life-threatening birth defects) of drug.1 (See Boxed Warning.)

  • Importance of taking lenalidomide only as prescribed, and in compliance with requirements of RevAssist program.1 (See Restricted Distribution Program under Dosage and Administration.)

  • Importance of providing patients with a copy of manufacturer’s patient information (medication guide) each time drug is dispensed.1 7 c j

  • Importance of warning women of childbearing potential not to take drug if pregnant, breast-feeding, or able to get pregnant (e.g., not using required methods of birth control).1

  • Necessity of advising any woman of childbearing potential to avoid pregnancy by using mandatory contraceptive measures, unless she abstains from heterosexual contact.1 (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of mandatory pregnancy testing prior to and during therapy.1

  • Importance of immediately discontinuing therapy if pregnancy suspected.1

  • Importance of women of childbearing potential informing clinicians of pregnancy, suspected pregnancy, missed menstrual period, unusual menstrual bleeding, or cessation of using contraceptive measures.1

  • Importance of informing patient how to obtain information about emergency contraception (including information regarding clinicians who provide emergency contraceptive services) if clinician not available.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of informing sexually mature male patients (including those who have undergone a vasectomy) of necessity of using a latex condom when engaging in sexual contact with a woman of childbearing potential or a pregnant woman.1 7 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of male patients informing clinicians of unprotected heterosexual sexual contact during therapy and for first 4 weeks after drug discontinuance.1 Importance of male patients informing clinician of suspected pregnancy of their sexual partner.1

  • Importance of informing patients not to share drug with anyone else (even if the other individual has similar symptoms) and of not donating blood or semen while receiving drug and for 4 weeks afterward.1 7 j

  • Importance of advising patients to swallow capsules whole with water, and not to break, chew, or open capsules.1 7

  • Importance of taking a missed dose as soon as possible, and not doubling the next dose.7

  • Risk of hematologic toxicities; importance of periodic monitoring of blood cell counts during treatment.1

  • Risk of venous thromboembolic events; importance of advising patients to immediately inform clinician if they develop symptoms of shortness of breath, chest pain, or swelling of the arms or legs.1 7 c

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 7

  • Importance of informing patients of other important precautionary information.1 7 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Distribution of lenalidomide is restricted.1 (See Restricted Distribution Program under Dosage and Administration.)

Lenalidomide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

5 mg

Revlimid

Celgene

10 mg

Revlimid

Celgene

15 mg

Revlimid

Celgene

25 mg

Revlimid

Celgene

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 7, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Celgene Corporation. Revlimid (lenalidomide) capsules prescribing information. Summit, NJ. 2007 Mar.

2. Greenberg P, Cox C, LeBeau MM et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997; 89:2079-88. [PubMed 9058730]

3. List A, Kurtin S, Roe DJ et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005; 352:549-57. [PubMed 15703420]

4. Hellstrom-Lindberg E. Update on supportive care and new therapies: Immunomodulatory drugs, growth factors and epigenetic-acting agents. In: Hematology. Washington, DC: American Society of Hematology; 2005:161-6.

5. List A, Dewald G, Bennett J et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006; 355:1456-65. [PubMed 17021321]

6. Food and Drug Administration. List of all orphan products designated and approved. From FDA web site (). Accessed 2007 Jan 25.

7. Celgene. Revlimid(lenalidomide) capsules patient medication guide. Summit, NJ. 2007 Mar.

8. Celgene Corporation, Summit, NJ: Personal communication.

20. Palumbo A, Rajkumar SV, Dimopoulos MA et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008; 22:414-23. [PubMed 18094721]

30. Raza A, Reeves JA, Feldman EJ et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008; 111:86-93. [PubMed 17893227]

31. Sekeres MA, Maciejewski JP, Giagounidis AA et al. Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2008; 26:5943-9. [PubMed 19018091]

32. A study of lenalidomide versus placebo in subjects with transfusion dependent anemia in low irsk myelodysplastic syndrome (MDS) without Del 5Q. From Clinical Trials (PDQ) database. Accessed 2013 Jan 30.

33. Cheson BD, Bennett JM, Kantarjian H et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000; 96:3671-4. [PubMed 11090046]

34. Cheson BD, Greenberg PL, Bennett JM et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006; 108:419-25. [PubMed 16609072]

35. AHFS off-label determination: Lenalidomide in transfusion-dependent low-risk or intermediate-1 risk myelodysplastic syndrome without the deletion 5q chromosomal abnormality. Published June 2013.

40. Celgene Corporation. Revlimid (lenalidomide) capsules prescribing information. Summit, NJ; 2013 Jun.

41. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: venous thromboembolic disease. Version 2.2013.

42. Lyman GH, Khorana AA, Kuderer NM et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013; 31:2189-204. [PubMed 23669224]

a. Maier SK, Hammond JM. Role of lenalidomide in the treatment of multiple myeloma and myelodysplastic syndrome. Ann Pharmacother. 2006; 40:286-9. [PubMed 16403850]

b. Nimer SD. Clinical management of myelodysplastic syndromes with interstitial deletion of chromosome 5q. J Clin Oncol. 2006; 24:2576-82. [PubMed 16735711]

c. Rao KV. Lenalidomide in the treatment of multiple myeloma. Am J Health-Syst Pharm. 2007; 64:1799-807. [PubMed 17724360]

d. Rajkumar SV, Hayman SR, Lacy MQ et al. Blood. 2005; 106:4050-3.

e. Lacy MQ, Gertz MA, Dispenzieri A et al. Mayo Clin Proc. 2007; 82:1179-84.

f. Chen N, Lau H, Kong L et al. J Clin Pharmacol. 2007; 47:1466-75.

g. Celgene Corporation. Thalomid (thalidomide) capsules prescribing information. Summit, NJ. 2007 Feb.

h. Hussein MA. Thromboembolic risk reduction in multiple myeloma patients treated with immunomodulatory drug combinations. Thromb Haemost. 2006; 95:924-30. [PubMed 16732369]

j. Celgene Corporation. Revlimid (lenalidomide). RevAssist At-A-Glance. March 2007. From web site (http://www.revlimid.com/hcp/hcp-revassist-pre.aspx).

l. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and lactation. 8th ed. Philadelphia, PA: Lippinoctt, Williams & Wilkins; 2008:1031-3.

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