IMPORTANT SAFETY INFORMATION ( CONTINUED )
Increased Mortality in Patients with CLL : In a clinical trial in the first-line treatment of patients with CLL , single agent REVLIMID therapy increased the risk of death as compared to single agent chlorambucil . Serious adverse cardiovascular reactions , including atrial fibrillation , myocardial infarction , and cardiac failure , occurred more frequently in the REVLIMID arm . REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials
Second Primary Malignancies ( SPM ): In clinical trials in patients with MM receiving REVLIMID , an increase of hematologic plus solid tumor SPM , notably AML and MDS have been observed . Monitor patients for the development of SPM . Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment
Hepatotoxicity : Hepatic failure , including fatal cases , has occurred in patients treated with REVLIMID / dex . Pre-existing viral liver disease , elevated baseline liver enzymes , and concomitant medications may be risk factors . Monitor liver enzymes periodically . Stop REVLIMID upon elevation of liver enzymes . After return to baseline values , treatment at a lower dose may be considered
Allergic Reactions : Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome ( SJS ) and toxic epidermal necrolysis ( TEN ) have been reported . These events can be fatal . Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID . REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash . REVLIMID must be discontinued 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 reactions . REVLIMID capsules contain lactose ; risk-benefit of treatment should be evaluated in patients with lactose intolerance
Tumor Lysis Syndrome ( TLS ): Fatal instances of TLS have been reported during treatment with lenalidomide . The patients at risk of TLS are those with high tumor burden prior to treatment . These patients should be monitored closely and appropriate precautions taken
Tumor Flare Reaction ( TFR ): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma . Monitoring and evaluation for TFR is recommended in patients with MCL . Tumor flare may mimic the progression of disease ( PD ). In patients with Grade 3 or 4 TFR , it is recommended to withhold treatment with REVLIMID until TFR resolves to ≤Grade 1 . REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification , at the physician ’ s discretion
Impaired Stem Cell Mobilization : A decrease in the number of CD34 + cells collected after treatment (> 4 cycles ) with REVLIMID has been reported . Consider early referral to transplant center to optimize timing of the stem cell collection
Thyroid Disorders : Both hypothyroidism and hyperthyroidism have been reported . Measure thyroid function before start of REVLIMID treatment and during therapy
ADVERSE REACTIONS
Multiple Myeloma
• Maintenance Therapy Post-Auto HSCT : The most frequently reported Grade 3 or 4 reactions in ≥20 % ( REVLIMID arm ) included neutropenia , thrombocytopenia , and leukopenia . The serious adverse reactions of lung infection and neutropenia ( more than 4.5 %) occurred in the REVLIMID arm
• The most frequently reported adverse reactions in ≥20 % ( REVLIMID arm ) across both maintenance studies ( Study 1 , Study 2 ) were neutropenia ( 79 %, 61 %), thrombocytopenia ( 72 %, 24 %), leukopenia ( 23 %, 32 %), anemia ( 21 %, 9 %), upper respiratory tract infection ( 27 %, 11 %), bronchitis ( 5 %, 47 %), nasopharyngitis ( 2 %, 35 %), cough ( 10 %, 27 %), gastroenteritis ( 0 %, 23 %), diarrhea ( 55 %, 39 %), rash ( 32 %, 8 %), fatigue ( 23 %, 11 %), asthenia ( 0 %, 30 %), muscle spasm ( 0 %, 33 %), and pyrexia ( 8 %, 21 %)
DRUG INTERACTIONS
Periodic monitoring of digoxin plasma levels is recommended due to increased C max and AUC with concomitant REVLIMID therapy . Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis . It is not known whether there is an interaction between dex and warfarin . Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin
USE IN SPECIFIC POPULATIONS
• PREGNANCY : See Boxed WARNINGS . If pregnancy does occur during treatment , immediately discontinue the drug and refer patient to an obstetrician / gynecologist experienced in reproductive toxicity for further evaluation and counseling . There is a REVLIMID pregnancy exposure registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy as well as female partners of male patients who are exposed to REVLIMID . This registry is also used to understand the root cause for the pregnancy . Report any suspected fetal exposure to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436
• LACTATION : There is no information regarding the presence of lenalidomide in human milk , the effects of REVLIMID on the breastfed infant , or the effects of REVLIMID on milk production . Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from REVLIMID , advise female patients not to breastfeed during treatment with REVLIMID
• PEDIATRIC USE : Safety and effectiveness have not been established in pediatric patients
• RENAL IMPAIRMENT : Adjust the starting dose of REVLIMID based on creatinine clearance value and in patients on dialysis
Please see Brief Summary of full Prescribing Information , including Boxed WARNINGS , on the following pages .
References
1 . Poon ML , Chng WJ . Is complete remission an important therapeutic aim in multiple myeloma ? Cancer Ther . 2008 ; 6:275-284 . 2 . Paiva B , Vidriales MB , Cervero J , et al . Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation . Blood . 2008 ; 112 ( 10 ): 4017-4023 . 3 . REVLIMID [ package insert ]. Summit , NJ : Celgene Corp ; 2017 . 4 . Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ® ) for Multiple Myeloma V . 3.2017 . © National Comprehensive Cancer Network , Inc . 2017 . All rights reserved . Accessed January 23 , 2017 . To view the most recent and complete version of the guideline , go online to NCCN . org .
5 . Data on file . Celgene Corp ; 2017 .
REVLIMID ® and REVLIMID REMS ® are registered trademarks of Celgene Corporation . © 2017 Celgene Corporation 03 / 17 US-REV170010a