Transcription

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to useLEMTRADA safely and effectively. See full prescribing information forLEMTRADA.LEMTRADA (alemtuzumab) injection, for intravenous useInitial U.S. Approval: 2001 WARNING: AUTOIMMUNITY, INFUSION REACTIONS,STROKE, AND MALIGNANCIESSee full prescribing information for complete boxed warning.LEMTRADA causes serious, sometimes fatal, autoimmuneconditions such as immune thrombocytopenia and anti glomerular basement membrane disease. Monitor complete bloodcounts with differential, serum creatinine levels, and urinalysiswith urine cell counts monthly until 48 months after the last dose.(5.1)LEMTRADA causes serious and life-threatening infusionreactions. LEMTRADA must be administered in a setting withappropriate equipment and personnel to manage anaphylaxis orserious infusion reactions. Monitor patients for two hours aftereach infusion. Make patients aware that serious infusion reactionscan also occur after the 2-hour monitoring period. (5.2)Serious and life-threatening stroke has been reported within 3days of LEMTRADA administration. Instruct patients to seekimmediate medical attention if symptoms of stroke occur. (5.3)LEMTRADA may cause an increased risk of malignancies,including thyroid cancer, melanoma, and lymphoproliferativedisorders. Perform baseline and yearly skin exams. (5.4)LEMTRADA is available only through a restricted distributionprogram. (5.5)---------------------------RECENT MAJOR CHANGES---------------------------- Boxed Warning09/2020Indications and Usage (1)10/2019Dosage and Administration, Infusion Instructions (2.5)09/2020Contraindications (4)09/2020Warnings and Precautions, Autoimmunity (5.1)09/2020Warnings and Precautions, Infusion Reactions (5.2)09/2020Warnings and Precautions, Thyroid Disorders (5.8)09/2020Warnings and Precautions, HLH (5.11)5/2020Warnings and Precautions, Acquired Hemophilia A (5.12)09/2020Warnings and Precautions, Infections S AND USAGE--------------------------- LEMTRADA is a CD52-directed cytolytic monoclonal antibody indicatedfor the treatment of relapsing forms of multiple sclerosis (MS), to includerelapsing-remitting disease and active secondary progressive disease, inadults. Because of its safety profile, the use of LEMTRADA shouldgenerally be reserved for patients who have had an inadequate response totwo or more drugs indicated for the treatment of MS [see Warnings andPrecautions (5)]. (1)Limitations of Use:LEMTRADA is not recommended for use in patients with clinicallyisolated syndrome (CIS) because of its safety profile [see Warnings andPrecautions (5)]. (1)----------------------DOSAGE AND ADMINISTRATION----------------------- Baseline laboratory tests are required prior to treatment. (2.1) Administer LEMTRADA by intravenous infusion over 4 hours for 2 ormore treatment courses:Initial treatment of 2 courses:o First course: 12 mg/day on 5 consecutive days. (2.3)o Second course: 12 mg/day on 3 consecutive days 12 months after firsttreatment course. (2.3)Reference ID: 4676303Subsequent treatment courses of 12 mg per day on 3 consecutive days (36mg total dose) may be administered, as needed, at least 12 months after thelast dose of any prior treatment course. (2.3) Premedicate with corticosteroids prior to LEMTRADA infusion for the first3 days of each treatment course. (2.2) Administer antiviral agents for herpetic prophylaxis starting on the first dayof LEMTRADA dosing and continuing for a minimum of two months aftercompletion of LEMTRADA dosing or until CD4 lymphocyte count ismore than 200 cells per microliter, whichever occurs later. (2.2) Must be diluted prior to administration. (2.4)---------------------DOSAGE FORMS AND STRENGTHS--------------------- Injection: 12 mg/1.2 mL (10 mg/mL) in a single-dose vial. ------------------------------ Known hypersensitivity or anaphylactic reactions to alemtuzumab or anyof the excipients in LEMTRADA(4) Infection with Human Immunodeficiency Virus (4) Active infection (4)------------------------WARNINGS AND PRECAUTIONS----------------------- Immune Thrombocytopenia: Obtain complete blood counts (CBCs) withdifferential prior to initiation of treatment and at monthly intervalsthereafter until 48 months after the last infusion. (5.6) Glomerular Nephropathies: Obtain serum creatinine levels, urinalysis withcell counts and urine protein to creatinine ratio prior to initiation oftreatment. Monitor serum creatinine levels and urinalysis with cell countsat monthly intervals thereafter until 48 months after the last infusion. (5.7) Thyroid Disorders: Obtain thyroid function tests prior to initiation oftreatment and every 3 months until 48 months after the last infusion. (5.8) Other Autoimmune Cytopenias: Monitor CBCs monthly until 48 monthsafter the last infusion. (2.6, 5.9) Autoimmune Hepatitis: If signs of hepatic dysfunction occur, promptlymeasure serum transaminases and total bilirubin and interrupt ordiscontinue treatment. (5.10) Hemophagocytic lymphohistiocytosis: Consider this diagnosis and evaluatepatients immediately if they develop signs or symptoms of systemicinflammation. Discontinue LEMTRADA if an alternative etiology is notestablished. (5.11) Acquired Hemophilia A: Obtain a coagulopathy panel including aPTT inpatients who present with signs such as spontaneous subcutaneoushematomas, extensive bruising, hematuria, epistaxis, or gastrointestinal orother types of bleeding. (5.12) Infections: Administration is contraindicated in patients with activeinfection. Do not administer live viral vaccines following a course ofLEMTRADA. (4, 5.13) Progressive Multifocal Leukoencephalopathy (PML): WithholdLEMTRADA at the first sign or symptom suggestive of PML. (5.14)------------------------------ADVERSE REACTIONS------------------------------ Most common adverse reactions (incidence 10% and interferon beta-1a):rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection,fatigue, insomnia, upper respiratory tract infection, herpes viral infection,urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain inextremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia,dizziness, abdominal pain, flushing, and vomiting. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact GenzymeCorporation at 1-800-745-4447 (option 2) or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.------------------------USE IN SPECIFIC POPULATIONS---------------------- Pregnancy: May cause fetal harm. (8.1)Women of childbearing potential should use effective contraception duringand for 4 months after a course of treatment with LEMTRADA. (8.3)See 17 for PATIENT COUNSELING INFORMATION and MedicationGuide.Revised: 09/2020

FULL PRESCRIBING INFORMATION: CONTENTS*WARNING: AUTOIMMUNITY, INFUSION REACTIONS, STROKE,AND MALIGNANCIES1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION2.1 Testing and Procedures Prior to Treatment2.2 Recommended Premedication and Concomitant Medication2.3 Recommended Dosage2.4 Preparation Instructions2.5 Infusion Instructions2.6 Laboratory Testing and Monitoring to Assess Safety3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Autoimmunity5.2 Infusion Reactions5.3 Stroke and Cervicocephalic Arterial Dissection5.4 Malignancies5.5 LEMTRADA REMS Program5.6 Immune Thrombocytopenia5.7 Glomerular Nephropathies Including Anti-glomerular BasementMembrane Disease5.8 Thyroid Disorders5.9 Other Autoimmune Cytopenias5.10 Autoimmune Hepatitis5.11 Hemophagocytic Lymphohistiocytosis5.12 Acquired Hemophilia A5.13 Infections5.14 Progressive Multifocal Leukoencephalopathy (PML)5.15 Acute Acalculous CholecystitisReference ID: 467630368101112131416175.16 Pneumonitis5.17 Drug Products with Same Active IngredientADVERSE REACTIONS6.1 Clinical Trials Experience6.2 Lymphopenia6.3 Suicidal Behavior or Ideation6.4 Immunogenicity6.5 Postmarketing ExperienceUSE IN SPECIFIC POPULATIONS8.1 Pregnancy8.2 Lactation8.3 Females and Males of Reproductive Potential8.4 Pediatric Use8.5 Geriatric UseOVERDOSAGEDESCRIPTIONCLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 PharmacokineticsNONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCLINICAL STUDIESHOW SUPPLIED/STORAGE AND HANDLING16.1 How Supplied16.2 Storage and HandlingPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are notlisted.

FULL PRESCRIBING INFORMATIONWARNING: AUTOIMMUNITY, INFUSION REACTIONS, STROKE, ANDMALIGNANCIES LEMTRADA causes serious, sometimes fatal, autoimmune conditions such asimmune thrombocytopenia and anti-glomerular basement membrane disease.Monitor complete blood counts with differential, serum creatinine levels, andurinalysis with urine cell counts before starting treatment and then at monthlyintervals until 48 months after the last dose of LEMTRADA [see Warnings andPrecautions (5.1)]. LEMTRADA causes serious and life-threatening infusion reactions. LEMTRADAmust be administered in a setting with appropriate equipment and personnel tomanage anaphylaxis or serious infusion reactions. Monitor patients for two hoursafter each infusion. Make patients aware that serious infusion reactions can alsooccur after the 2-hour monitoring period [see Warnings and Precautions (5.2)]. Serious and life-threatening stroke (including ischemic and hemorrhagic stroke) hasbeen reported within 3 days of LEMTRADA administration. Instruct patients to seekimmediate medical attention if symptoms of stroke occur [see Warnings andPrecautions (5.3)]. LEMTRADA may cause an increased risk of malignancies, including thyroid cancer,melanoma, and lymphoproliferative disorders. Perform baseline and yearly skinexams [see Warnings and Precautions (5.4)]. Because of the risk of autoimmunity, infusion reactions, and malignancies,LEMTRADA is available only through restricted distribution under a RiskEvaluation Mitigation Strategy (REMS) Program. Call 1-855-676-6326 to enroll inthe LEMTRADA REMS program [see Warnings and Precautions (5.5)].1INDICATIONS AND USAGELEMTRADA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), toinclude relapsing-remitting disease and active secondary progressive disease, in adults. Becauseof its safety profile, the use of LEMTRADA should generally be reserved for patients who havehad an inadequate response to two or more drugs indicated for the treatment of MS [see Warningsand Precautions (5)].Limitations of UseLEMTRADA is not recommended for use in patients with clinically isolated syndrome (CIS)because of its safety profile [see Warnings and Precautions (5)].2DOSAGE AND ADMINISTRATION2.1Testing and Procedures Prior to Treatment3Reference ID: 4676303

Baseline laboratory tests are required prior to treatment with LEMTRADA [see Dosage andAdministration (2.6)]. In addition, prior to starting treatment with LEMTRADA [see Warningsand Precautions (5.12)]: complete any necessary immunizations at least 6 weeks prior to treatment. determine whether patients have a history of varicella or have been vaccinated for varicellazoster virus (VZV). If not, test the patient for antibodies to VZV and consider vaccinationfor those who are antibody-negative. Postpone treatment with LEMTRADA until 6 weeksafter VZV vaccination. perform tuberculosis screening according to local guidelines. instruct patients to avoid potential sources of Listeria monocytogenes.2.2Recommended Premedication and Concomitant MedicationCorticosteroidsPremedicate patients with high dose corticosteroids (1,000 mg methylprednisolone or equivalent)immediately prior to LEMTRADA infusion and for the first 3 days of each treatment course [seeWarnings and Precautions (5.2)].Herpes ProphylaxisAdminister antiviral prophylaxis for herpetic viral infections starting on the first day of eachtreatment course and continue for a minimum of two months following treatment withLEMTRADA or until the CD4 lymphocyte count is at least 200 cells per microliter, whicheveroccurs later [see Warnings and Precautions (5.12)].2.3 Recommended DosageThe recommended dosage of LEMTRADA is 12 mg/day administered by intravenousinfusion for 2 treatment courses: First Treatment Course: 12 mg/day on 5 consecutive days(60 mg total dose).Second Treatment Course: 12 mg/day on 3 consecutive days (36 mg total dose) administered12 months after the first treatment course.Following the second treatment course, subsequent treatment courses of 12 mg per day on 3consecutive days (36 mg total dose) may be administered, as needed, at least 12 months after thelast dose of any prior treatment courses.2.4Preparation InstructionsFollow the steps below to prepare the diluted solution of LEMTRADA for intravenous infusion: Inspect LEMTRADA visually for particulate matter and discoloration prior toadministration. Do not use if particulate matter is present or the solution is discolored. Donot freeze or shake vials prior to use.Withdraw 1.2 mL of LEMTRADA from the vial into a syringe using aseptic techniqueand inject into a 100 mL bag of sterile 0.9% Sodium Chloride, USP or 5% Dextrose inWater, USP.4Reference ID: 4676303

Gently invert the bag to mix the solution. Ensure the sterility of the prepared solution,because it contains no antimicrobial preservatives. Each vial is for single use only.Prior to administration, protect diluted LEMTRADA solution from light and store for as long as 8hours either at room temperature 15 C to 25 C (59 F to 77 F) or keep refrigerated at conditions2 C to 8 C (36 F to 46 F).2.5Infusion InstructionsInfuse LEMTRADA over 4 hours starting within 8 hours after dilution. Extend the duration of theinfusion if clinically indicated.Administer LEMTRADA in a setting in which equipment and personnel to appropriately manageanaphylaxis, serious infusion reactions, myocardial ischemia, myocardial infarction, andcerebrovascular and respiratory adverse reactions are available [see Warnings and Precautions(5.2)].Do not add or simultaneously infuse other drug substances through the same intravenous line. Donot administer as an intravenous push or bolus.Obtain a baseline ECG. Monitor vital signs before the infusion and periodically during theinfusion. Provide appropriate symptomatic treatment for infusion reactions as needed. Considerimmediate discontinuation of the intravenous infusion if severe infusion reactions occur.Observe patients for infusion reactions during and for at least 2 hours after each LEMTRADAinfusion. Consider longer periods of observation if clinically indicated. Inform patients that theyshould report symptoms that occur during and after each infusion because they may indicate a needfor prompt medical intervention [see Warnings and Precautions (5.2)].2.6Laboratory Testing and Monitoring to Assess SafetyMeasure the urine protein to creatinine ratio prior to initiation of treatment. Conduct the followinglaboratory tests at baseline and at periodic intervals until 48 months after the last treatment courseof LEMTRADA in order to monitor for early signs of potentially serious adverse effects: Complete blood count (CBC) with differential (prior to treatment initiation and atmonthly intervals thereafter)Serum creatinine levels (prior to treatment initiation and at monthly intervals thereafter)Urinalysis with urine cell counts (prior to treatment initiation and at monthly intervalsthereafter)A test of thyroid function, such as thyroid stimulating hormone (TSH) level (prior totreatment initiation and every 3 months thereafter)Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase[AST]) and total bilirubin levels (prior to treatment initiation and periodically thereafter)Conduct baseline and yearly skin exams to monitor for melanoma [see Warnings and Precautions(5.4)].3DOSAGE FORMS AND STRENGTHS5Reference ID: 4676303

Injection: 12 mg/1.2 mL (10 mg/mL) in a single-dose vial. LEMTRADA is a clear and colorlessto slightly yellow solution that requires dilution prior to intravenous infusion.4CONTRAINDICATIONSLEMTRADA is contraindicated in patients: with known hypersensitivity or anaphylactic reactions to alemtuzumab or any of theexcipients in LEMTRADA who are infected with human immunodeficiency virus (HIV) because LEMTRADA causesprolonged reductions of CD4 lymphocyte counts with active infection5WARNINGS AND PRECAUTIONS5.1AutoimmunityTreatment with LEMTRADA can result in the formation of autoantibodies and increase the riskof serious autoimmune mediated conditions, which may be life threatening.In clinical studies (controlled and open-label extension), LEMTRADA-treated patientsexperienced thyroid disorders (36.8%), immune thrombocytopenia (2%), and glomerularnephropathies (0.3%) [see Warnings and Precautions (5.7, 5.8, 5.9)]. Vitiligo and autoimmunehemolytic anemia occurred in 0.3% of patients. Autoimmune pancytopenia [see Warnings andPrecautions (5.9)], undifferentiated connective tissue disorders, and type 1 diabetes each occurredin 0.2% of patients. Rheumatoid arthritis, retinal pigment epitheliopathy, and acquired hemophiliaA (anti-Factor VIII antibodies) [see Warnings and Precautions (5.12)] occurred in 0.1% ofpatients. During postmarketing use, cases of vasculitis, autoimmune hepatitis [see Warnings andPrecautions (5.10)], and Guillain-Barré syndrome have been reported [see Adverse Reactions(6.5)].Chronic inflammatory demyelinating polyradiculoneuropathy has been reported in the treatmentof patients with B-cell chronic lymphocytic leukemia (B-CLL), as well as other autoimmunedisorders, generally at higher and more frequent doses than recommended in MS. An oncologypatient treated with alemtuzumab had fatal transfusion-associated graft-versus-host disease.Autoantibodies may be transferred from the mother to the fetus during pregnancy. A case oftransplacental transfer of anti-thyrotropin receptor antibodies resulting in neonatal Graves’ diseaseoccurred after alemtuzumab treatment in the mother [see Use in Specific Populations (8.1)].LEMTRADA may increase the risk of other autoimmune conditions because of the broad range ofautoantibody formation with LEMTRADA.Measure the urine protein to creatinine ratio prior to initiation of treatment. Monitor completeblood counts with differential, serum creatinine levels, and urinalysis with urine cell counts beforestarting treatment and then at monthly intervals until 48 months after the last dose of LEMTRADAto allow for early detection and treatment of autoimmune adverse reactions [see Dosage andAdministration (2.6)]. After 48 months, testing should be performed based on clinical findingssuggestive of autoimmunity.6Reference ID: 4676303

LEMTRADA is available only through a restricted program under a REMS [see Warnings andPrecautions (5.5)].5.2Infusion ReactionsLEMTRADA causes cytokine release syndrome resulting in infusion reactions, some of whichmay be serious and life threatening. In clinical studies, 92% of LEMTRADA-treated patientsexperienced infusion reactions. In some patients, infusion reactions were reported more than 24hours after LEMTRADA infusion. Serious reactions occurred in 3% of patients and includedanaphylaxis in 2 patients (including anaphylactic shock), angioedema, bronchospasm,hypotension, chest pain, bradycardia, tachycardia (including atrial fibrillation), transientneurologic symptoms, hypertension, headache, pyrexia, and rash. Other infusion reactionsincluded nausea, urticaria, pruritus, insomnia, chills, flushing, fatigue, dyspnea, pulmonaryinfiltrates, dysgeusia, dyspepsia, dizziness, and pain. In clinical studies, 0.6% of patients withinfusion reactions received epinephrine or atropine.During postmarketing use, cases of pulmonary alveolar hemorrhage, myocardial ischemia,myocardial infarction, stroke (including ischemic and hemorrhagic stroke), and cervicocephalic(e.g., vertebral, carotid) arterial dissection have been reported. Reactions may occur followingany of the doses during the treatment course. In the majority of cases, time to onset was within 1to 3 days of LEMTRADA infusion. Patients should be informed about the signs and symptomsand advised to seek immediate medical attention if any of these symptoms occur. Cases of severe(including fatal) neutropenia have been reported within 2 months of LEMTRADA infusion;some cases resolved with receiving granulocyte-colony stimulating factor treatment. Mild tomoderate decreases in platelet counts, starting at the time of alemtuzumab infusion and oftenresolving without treatment, have been reported. Other serious and sometimes fatal infusionreactions (e.g., hypoxia, syncope, acute respiratory distress syndrome, respiratory arrest,myocardial infarction, acute cardiac insufficiency, cardiac arrest) have been reported in thetreatment of patients with B-CLL, as well as other disorders, generally at higher and morefrequent doses than recommended in MS.Premedicate patients with corticosteroids immediately prior to LEMTRADA infusion for the first3 days of each treatment course. In clinical studies, patients received 1,000 mg ofmethylprednisolone for the first 3 days of each LEMTRADA treatment course. Considerpretreatment with antihistamines and/or antipyretics prior to LEMTRADA administration.Infusion reactions may occur despite pretreatment.Consider additional monitoring in patients with medical conditions which predispose them tocardiovascular or pulmonary compromise. Physicians should alert patients that an infusionreaction could occur within 48 hours of infusion.LEMTRADA can only be administered in certified healthcare settings that have on-site access toequipment and personnel trained to manage infusion reactions (including anaphylaxis,cerebrovascular, cardiac and respiratory emergencies) [see Dosage and Administration (2.5)].LEMTRADA is available only through a restricted program under a REMS [see Warnings andPrecautions (5.5)].5.3Stroke and Cervicocephalic Arterial Dissection7Reference ID: 4676303

StrokeIn the postmarketing setting, serious and life-threatening stroke (including ischemic andhemorrhagic stroke) has been reported within 3 days of LEMTRADA administration, with mostcases occurring within 1 day.Cervicocephalic Arterial DissectionIn the postmarketing setting, cases of cervicocephalic (e.g., vertebral, carotid) arterial dissectioninvolving multiple arteries have been reported within 3 days of LEMTRADA administration.Ischemic stroke was reported in one of these cases.Educate patients on the symptoms of stroke and cervicocephalic (e.g., carotid, vertebral) arterialdissection. Instruct patients to seek immediate medical attention if symptoms of stroke orcervicocephalic arterial dissection occur.5.4MalignanciesThyroid CancerLEMTRADA may increase the risk of thyroid cancer. In controlled clinical studies, 3 of 919(0.3%) LEMTRADA-treated patients developed thyroid cancer, compared to none in the interferonbeta-1a–treated group. However, screening for thyroid cancer was performed more frequently inthe LEMTRADA-treated group, because of the higher incidence of autoimmune thyroid disordersin those patients. Two additional cases of thyroid cancer in LEMTRADA-treated patients occurredin uncontrolled studies.Patients and healthcare providers should monitor for symptoms of thyroid cancer including a newlump or swelling in the neck, pain in the front of the neck, persistent hoarseness or other voicechanges, trouble swallowing or breathing, or a constant cough not due to an upper respiratory tractinfection.MelanomaLEMTRADA may increase the risk of melanoma. In MS clinical studies (controlled and openlabel extension), 5 of 1486 (0.3%) LEMTRADA-treated patients developed melanoma ormelanoma in situ. One of those patients had evidence of locally advanced disease.Perform baseline and yearly skin examinations to monitor for melanoma in patients receivingLEMTRADA.Lymphoproliferative Disorders and LymphomaCases of lymphoproliferative disorders and lymphoma have occurred in LEMTRADA-treatedpatients with MS, including a MALT lymphoma, Castleman’s Disease, and a fatality followingtreatment of non-Epstein Barr Virus–associated Burkitt’s lymphoma. There are postmarketingreports of Epstein Barr Virus–associated lymphoproliferative disorders in non-MS patients.Because LEMTRADA is an immunomodulatory therapy, caution should also be exercised ininitiating LEMTRADA in patients with preexisting or ongoing malignancies.LEMTRADA is available only through a restricted program under a REMS [see Warnings andPrecautions (5.5)].5.5LEMTRADA REMS Program8Reference ID: 4676303

LEMTRADA is available only through a restricted program under a REMS called theLEMTRADA REMS Program because of the risks of autoimmunity, infusion reactions, andmalignancies [see Warnings and Precautions (5.1, 5.2, 5.4)].Notable requirements of the LEMTRADA REMS Program include the following: Prescribers must be certified with the program by enrolling and completing training.Patients must enroll in the program and comply with ongoing monitoring requirements[see Dosage and Administration (2.6)].Pharmacies must be certified with the program and must only dispense to certifiedhealthcare facilities that are authorized to receive LEMTRADA.Healthcare facilities must enroll in the program and verify that patients are authorizedbefore infusing LEMTRADA. Healthcare facilities must have on-site access toequipment and personnel trained to manage infusion reactions.Further information, including a list of qualified healthcare facilities, is available at 1-855-676 6326.5.6Immune ThrombocytopeniaImmune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients in MS clinicalstudies (controlled and open-label extension).In a controlled clinical study in patients with MS, one LEMTRADA-treated patient developed ITPthat went unrecognized prior to the implementation of monthly blood monitoring requirements,and died from intracerebral hemorrhage. Nadir platelet counts 20,000 cells per microliter as aresult of ITP occurred in 2% of all LEMTRADA-treated patients in clinical studies in MS. Antiplatelet antibodies did not precede ITP onset. ITP has been diagnosed more than 3 years after thelast LEMTRADA dose.Symptoms of ITP include easy bruising, petechiae, spontaneous mucocutaneous bleeding (e.g.,epistaxis, hemoptysis), and heavier than normal or irregular menstrual bleeding. Hemoptysis mayalso be indicative of anti-glomerular basement membrane (GBM) disease [see Warnings andPrecautions (5.7)], and an appropriate differential diagnosis has to be undertaken. Remind thepatient to remain vigilant for symptoms they may experience and to seek immediate medical helpif they have any concerns.Obtain complete blood counts (CBCs) with differential prior to initiation of treatment and atmonthly intervals thereafter until 48 months after the last infusion [see Dosage and Administration(2.6)]. After this period of time, testing should be performed based on clinical findings suggestiveof ITP. If ITP is suspected, a complete blood count should be obtained immediately. If ITP onsetis confirmed, promptly initiate appropriate medical intervention.5.7Glomerular Nephropathies Including Anti-glomerular Basement MembraneDiseaseGlomerular nephropathies occurred in 0.3% of LEMTRADA-treated patients in MS clinicalstudies. There were 3 cases of membranous glomerulonephritis and 2 cases of anti-glomerularbasement membrane (anti-GBM) disease.9Reference ID: 4676303

In postmarketing cases, some LEMTRADA-treated patients with anti-GBM disease developedend-stage renal disease requiring dialysis or renal transplantation. Urgent evaluation and treatmentare required because early treatment can improve the preservation of renal function. Anti-GBMdisease can be life-threatening if left untreated. Alveolar hemorrhage, manifested as hemoptysis,is a common component of anti-GBM disease and has been reported in postmarketing cases. Casesof anti-GBM disease have been diagnosed up to 40 months after the last dose of LEMTRADA.Symptoms of nephropathy may include edema, hematuria, change in urine color, decreased urineoutput, fatigue, dyspnea, and hemoptysis. Patients and caregivers should be instructed to seekmedical advice if they have concerns.Obtain serum creatinine levels, urinalysis with cell counts, and urine protein to creatinine ratioprior to initiation of treatment. Obtain serum creatinine levels and urinalysis with cell counts atmonthly intervals thereafter until 48 months after the last infusion. After this period of time, testingshould be performed based on clinical findings suggestive of nephropathies.For urine dipstick results of 1 protein or greater, measure the urine protein to creatinine ratio. Forurine protein to creatinine ratio greater than 200 mg/g, increase in serum creatinine greater than30%, or unexplained hematuria, perform further evaluation for nephropathies. Increased serumcreatinine with hematuria or signs of pulmonary involvement of anti-GBM disease (e.g.,hemoptysis, exertional dyspnea) warrant immediate evaluation. Early detection and treatment ofnephropathies may decrease the risk of poor outcomes.5.8Thyroid DisordersThyroid endocrine disorders, including autoimmune thyroid disorders, occurred in 36.8% ofLEMTRADA-treated patients in MS clinical studies (controlled and open-label extension). Newlydiagnosed thyroid disorders occurred throughout the uncontrolled clinical study follow-up period,more than 7 years after the first LEMTRADA dose. Autoimmune thyroid disorders includedGraves’ disease, hyperthyroidism, hypothyroidism, autoimmune thyroiditis, and goiter. Graves’ophthalmopathy with decreased vision, eye pain, and exophthalmos occurred in 2% ofLEMTRADA-treated patients. Seven patients required surgical orbital decompression. Seriousthyroid events occurred in about 5.2% of LEMTRADA-treated pa

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use LEMTRADA safely and effectively. See full prescribing information for LEMTRADA. LEMTRADA (alemtuzumab) injection, for intravenous use Initial U.S. Approval: 2001 .