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Drugs reference index «Lenalidomide»

Lenalidomide
Lenalidomide


Lenalidomide

Pronunciation: (LEN-a-LID-oh-mide)Class: Immunologic agent

Trade Names:Revlimid- Capsules 5 mg- Capsules 10 mg- Capsules 15 mg- Capsules 25 mg

Pharmacology

Possesses antineoplastic, immunomodulatory, and antiangiogenic properties. Inhibits the secretion of proinflammatory cytokines and increases the secretion of anti-inflammatory cytokines.

Pharmacokinetics

Absorption

Rapidly absorbed following oral administration, with C max occurring 0.625 to 1.5 h postdose. Food reduces C max 36%. The pharmacokinetic disposition is linear; C max and AUC increase proportionately with dose. In multiple myeloma patients, C max occurred 0.5 to 4 h after administration.

Distribution

Plasma protein binding is approximately 30%.

Metabolism

Has not been studied

Elimination

Approximately 67% is excreted unchanged in the urine and exceeds glomerular filtration rate, indicating elimination is partially or entirely active. The half-life is about 3 h.

Special Populations

Renal Function Impairment

The AUC was 56% greater in multiple myeloma patients with mild renal function impairment compared with healthy 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 function impairment compared with healthy subjects.

Hepatic Function Impairment

Pharmacokinetics have not been studied in patients with hepatic function impairment.

Elderly

Effects of age on pharmacokinetics have not been studied.

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 (MDS) 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.

Unlabeled Uses

Behçet syndrome.

Contraindications

Pregnancy; women capable of becoming pregnant; hypersensitivity to any component of the product.

Dosage and Administration

MDSAdults

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 was 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 and 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 and platelet transfusions, then resume lenalidomide at 5 mg every other day 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 ANC 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 5 mg every other day when neutrophils return to 500/mcL or more.

Multiple MyelomaAdults

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 orally 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, 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, 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 ImpairmentAdults

PO Starting dose adjustments for renal function impairment. After initiation of therapy, subsequent dose modification should be based on individual patient treatment tolerance.

Multiple myeloma Moderate renal function impairment (CrCl 30 to less than 60 mL/min)

Administer 10 mg every 24 h.

Severe renal function impairment (CrCl less than 30 mL/min [not requiring dialysis])

Administer 15 mg every 48 h.

End stage renal disease (CrCl less than 30 mL/min [requiring dialysis])

Administer 5 mg once daily. On dialysis days, administer the dose following dialysis.

Myelodysplastic syndromes Moderate renal function impairment (CrCl 30 to less than 60 mL/min)

Administer 5 mg every 24 h.

Severe renal function impairment (CrCl less than 30 mL/min [not requiring dialysis])

Administer 5 mg every 48 h.

End stage renal disease (CrCl less than 30 mL/min [requiring dialysis])

Administer 5 mg 3 times a wk following each dialysis.

General Advice

  • Administer prescribed 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.

Storage/Stability

Store capsules at 59° to 86°F.

Drug Interactions

Digoxin

Digoxin C max is increased 14% with coadministration.

Food

Coadministration with food does not affect the extent of absorption but does decrease the C max 36%. However, lenalidomide may be taken without regard to meals.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (6%); palpitations (5%); aggravated atrial fibrillation, angina pectoris, aortic disorder, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, cardiogenic shock, cardiomyopathy, cardiorespiratory arrest, congestive cardiac failure, deep vein thrombosis (DVT), hypotension, ischemia, MI, myocardial ischemia, pulmonary edema, superficial thrombophlebitis, supraventricular arrhythmia, tachyrhythmia, thrombosis, transient ischemic attack, ventricular dysfunction.

CNS

Fatigue (31%); pyrexia (21%); dizziness, headache (20%); asthenia (15%); insomnia (10%); hyposthesia (7%); dysgeusia (6%); depression, peripheral neuropathy (5%); abnormal gait, aphasia, cerebellar infarction, cerebrovascular accident, confusional state, depressed level of consciousness, dysarthria, migraine, spinal cord compression, subarachnoid hemorrhage.

Dermatologic

Pruritus (42%); rash (36%); dry skin (14%); contusion, night sweats (8%); increased sweating (7%); ecchymosis, erythema (5%); acute febrile neutrophilic dermatosis.

EENT

Nasopharyngitis (23%); pharyngitis (16%); rhinitis (7%); ear infection, vertigo.

Endocrine

Hypothyroidism (7%); Basedow disease, dehydration, gout, hypernatremia, hypoglycemia.

GI

Diarrhea (49%); constipation, nausea (24%); abdominal pain (12%); vomiting (10%); upper abdominal pain (8%); dry mouth (7%); 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.

Genitourinary

UTI (11%); dysuria (7%), azotemia, blood creatinine increase, hematuria, kidney infection, renal failure, renal mass, ureteric calculus.

Hematologic-Lymphatic

Thrombocytopenia (62%); neutropenia (59%); anemia (12%); leukopenia (8%); febrile neutropenia (5%); bone marrow depression, coagulopathy, hemoglobin decreased, hemolysis, hemolytic anemia, refractory anemia, splenic infarction, warm-type hemolytic anemia.

Hepatic

Acute cholecystitis, cholecystitis, hepatic failure, hyperbilirubinemia, LFTs abnormal.

Lab Tests

Increased ALT (8%); troponin Ι increased.

Metabolic-Nutritional

Hypokalemia (11%); anorexia (10%); hypomagnesemia (6%).

Musculoskeletal

Arthralgia (22%); back pain (21%); muscle cramp (18%); limb pain (11%); myalgia (9%); peripheral swelling (8%); rigors (6%); arthritis, bone fractures, chondrocalcinosis pyrophosphate, fall, gouty arthritis, neck pain.

Respiratory

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.

Miscellaneous

Peripheral edema (20%); edema (10%); pain (7%); cellulitis, chest pain (5%); bacteremia, central line infection, clostridial infection, disease progression (culture negative), Enterobacter sepsis, fungal infection, 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.

Precautions

Warnings

DVT and pulmonary embolism (PE)

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 MDS. 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. Lenalidomide is only available under a restricted distribution system in which only health care providers and pharmacists registered with the program are able to prescribe and dispense lenalidomide; only patients who are registered and meet all the requirements of the program are able to receive the medication.

Monitor

Perform CBC, including WBC count with differential, platelet count, Hgb, and Hct, weekly for first 8 wk of therapy and at least monthly thereafter to monitor for cytopenias.

Pregnancy

Category X .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Patients 65 yr of age 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.

Renal Function

Risk of adverse reactions may be increased. Take care with dose selection and monitor renal function.

Angioedema

Has been reported.

Dermatologic events

Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. These events are serious and can be fatal.

Men

Contraindicated 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 understanding of these warnings and of 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 yr of age.

Pregnancy testing

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.

Tumor lysis syndrome

Because lenalidomide has antineoplastic activity, complications of tumor lysis syndrome may occur.

Women

Contraindicated 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 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; parent or legal guardian reads the educational materials and agrees to try to ensure compliance with above for patients between 12 and 18 yr of age.

Overdosage

Symptoms

None reported.

Patient Information

  • Review guidelines and requirements for participation in the RevAssist program with patient or caregiver.
  • Advise patient or caregiver to read the Medication Guide carefully before starting therapy and to read each time the medication is refilled.
  • Advise patient 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 patient 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 patient to take prescribed dose with a glass of water once daily. Advise patient that medication can be taken without regard to meals but to take with food if stomach upset occurs.
  • Caution patient to swallow capsules whole and not to break, chew, or open the capsules.
  • Instruct patient 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 patient, family, or caregiver to notify health care provider if rash, hives, persistent diarrhea, or excessive or unexplained tiredness develop.
  • Advise patient that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Advise women 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.

Copyright © 2009 Wolters Kluwer Health.

  • Lenalidomide MedFacts Consumer Leaflet (Wolters Kluwer)
  • lenalidomide Advanced Consumer (Micromedex) - Includes Dosage Information
  • Revlimid Prescribing Information (FDA)
  • Revlimid Consumer Overview

See Also...

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