Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 09 February 2018

Indication(s)

1 INDICATIONS AND USAGE LEMTRADA is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of LEMTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS. LEMTRADA is a CD52-directed cytolytic monoclonal antibody indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of LEMTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS. (1)

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Advisory information

contraindications
4 CONTRAINDICATIONS LEMTRADA is contraindicated in patients who are infected with Human Immunodeficiency Virus (HIV) because LEMTRADA causes prolonged reductions of CD4+ lymphocyte counts. Infection with Human Immunodeficiency Virus. (4)
Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Autoimmunity [see Boxed Warning and Warnings and Precautions (5.1)] Infusion Reactions [see Boxed Warning and Warnings and Precautions (5.2)] Malignancies [see Warnings and Precautions (5.3)] Immune Thrombocytopenia [see Warnings and Precautions (5.5)] Glomerular Nephropathies [see Warnings and Precautions (5.6)] Thyroid Disorders [see Warnings and Precautions (5.7)] Other Autoimmune Cytopenias [see Warnings and Precautions (5.8)] Infections [see Warnings and Precautions (5.9)] Acute Acalculous Cholecystitis [see Warnings and Precautions (5.10)] Pneumonitis [see Warnings and Precautions (5.11)] 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 in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-800-745-4447 (option 2) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In controlled clinical trials (Study 1 and Study 2), a total of 811 patients with relapsing forms of MS received LEMTRADA. A total of 811 patients received 1 course of therapy, and 789 patients received a second course of therapy at 12 months. The overall follow-up in the controlled trials was equivalent to 1622 patient years, with an additional 3411 person-years of follow-up in an open-label extension study. The population was 18-55 years of age, 65% were female, and 92% were Caucasian. Most Common Adverse Reactions In clinical trials, the most common adverse reactions with LEMTRADA (in at least 10% of patients and more frequently than in interferon beta-1a) were 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 in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. Table 1 lists adverse reactions occurring in ≥5% of LEMTRADA-treated patients in Study 1 and 2 and at the same or at a higher rate than interferon beta-1a. Table 1: Adverse Reactions in the Pooled 2-Year Active-Controlled Studies in Patients with Relapsing-Remitting Multiple Sclerosis LEMTRADA (N=811) % interferon beta-1a 44 mcg (N=389) % Rash 53 6 Headache 52 23 Pyrexia 29 9 Nasopharyngitis 25 19 Nausea 21 9 Urinary tract infection 19 8 Fatigue 18 13 Insomnia 16 15 Upper respiratory tract infection 16 13 Herpes viral infection 16 3 Urticaria 16 2 Pruritus 14 2 Thyroid gland disorders 13 3 Fungal infection 13 4 Arthralgia 12 9 Pain in extremity 12 9 Back pain 12 8 Diarrhea 12 6 Sinusitis 11 8 Oropharyngeal pain 11 5 Paresthesia 10 8 Dizziness 10 5 Abdominal pain 10 5 Flushing 10 4 Vomiting 10 3 Cough 9 4 Chills 9 3 Dysgeusia 8 7 Influenza 8 6 Dermatitis 8 5 Dyspepsia 8 4 Blood in urine 8 3 Dyspnea 8 1 Tachycardia 8 1 Anxiety 7 6 Muscular weakness 7 6 Bronchitis 7 4 Chest discomfort 7 2 Muscle spasms 6 5 Myalgia 6 5 Decrease in CD4 lymphocytes 6 2 Decrease in CD8 lymphocytes 6 2 Asthenia 5 4 Decrease in T-lymphocyte count 5 3 Erythema 5 2 Peripheral edema 5 2 Epistaxis 5 2 Neck Pain 5 2 Abnormal uterine bleeding 5 1 6.2 Lymphopenia Nearly all (99.9%) patients treated with LEMTRADA in MS clinical trials experienced lymphopenia. The lowest lymphocyte counts occurred approximately by 1 month after each course of treatment. The mean lymphocyte count at 1 month after LEMTRADA treatment was 0.25 × 109 L (range 0.02-2.30 × 109 L) and 0.32 (0.02-1.81 × 109 L) for treatment courses 1 and 2, respectively. Total lymphocyte counts increased to reach the lower limit of normal in approximately 40% of patients by 6 months after each LEMTRADA treatment course and approximately 80% of patients by 12 months after each course [see Clinical Pharmacology (12.2)]. 6.3 Suicidal Behavior or Ideation In clinical studies, 0.6% of patients in both the LEMTRADA and interferon beta-1a groups had events of attempted suicide or suicidal ideation. There were no completed suicides in either clinical study treatment group. Suicidal behavior or ideation occurred in patients with or without a history of a psychiatric or thyroid disorder. Advise patients to report immediately any symptoms of depression or suicidal ideation to the prescribing physician. 6.4 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. Using an enzyme-linked immunosorbent assay (ELISA) and a competitive binding assay, anti-alemtuzumab binding antibodies were detected in 62%, 67%, and 29% of LEMTRADA-treated patients, at months 1, 3, 12 (Course 1) as well as 83%, 83%, and 75% of LEMTRADA-treated patients at months 13, 15, and 24 (Course 2). Samples that tested positive for binding antibodies were further evaluated for evidence of in vitro inhibition using a flow cytometry assay. Neutralizing antibodies were detected in 87%, 46%, and 5% of positive binding antibody patients at months 1, 3, 12 (Course 1) as well as 94%, 88%, and 42% of positive binding antibody patients at months 13, 15, and 24 (Course 2). Anti-alemtuzumab antibodies were associated with decreased alemtuzumab concentration during Course 2 but not Course 1. There was no evidence from clinical trials that the presence of binding or inhibitory anti-alemtuzumab antibodies had a significant effect on clinical outcomes, total lymphocyte count, or adverse events. The incidence of antibodies is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including inhibitory antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to LEMTRADA with the incidence of antibodies to other products may be misleading. 6.5 Postmarketing Experience The following adverse reactions have been identified during post-approval use of alemtuzumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Postmarketing Experience with LEMTRADA Gastrointestinal System Disorders: Acute acalculous cholecystitis. Postmarketing Experience with CAMPATH CAMPATH is approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) and is generally administered at higher and more frequent doses (e.g., 30 mg) than recommended in the treatment of MS. Cardiac Disorders: Congestive heart failure, cardiomyopathy, and decreased ejection fraction in non-MS patients previously treated with potentially cardiotoxic agents.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Administer LEMTRADA by intravenous infusion over 4 hours for 2 treatment courses: First course: 12 mg/day on 5 consecutive days. (2.1) Second course: 12 mg/day on 3 consecutive days 12 months after first treatment course. (2.1) Premedicate with corticosteroids prior to LEMTRADA infusion for the first 3 days of each treatment course. (2.3) Administer antiviral agents for herpetic prophylaxis starting on the first day of LEMTRADA dosing and continuing for a minimum of two months after completion of LEMTRADA dosing or until CD4+ lymphocyte count is more than 200 cells per microliter, whichever occurs later. (2.3) Must be diluted prior to administration. (2.4) 2.1 Dosage Information The recommended dosage of LEMTRADA is 12 mg/day administered by intravenous infusion 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) administered 12 months after the first treatment course. 2.2 Testing and Procedures Prior to Treatment Baseline laboratory tests are required prior to treatment with LEMTRADA [see Dosage and Administration (2.6)]. In addition, prior to starting treatment with LEMTRADA [see Warnings and Precautions (5.9)]: complete any necessary immunizations at least 6 weeks prior to treatment determine whether patients have a history of varicella or have been vaccinated for varicella zoster virus (VZV). If not, test the patient for antibodies to VZV and consider vaccination for those who are antibody-negative. Postpone treatment with LEMTRADA until 6 weeks after VZV vaccination. perform tuberculosis screening according to local guidelines. instruct patients to avoid potential sources of Listeria monocytogenes. 2.3 Recommended Premedication and Concomitant Medication Corticosteroids Premedicate 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 [see Warnings and Precautions (5.2)]. Herpes Prophylaxis Administer anti-viral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with LEMTRADA or until the CD4+ lymphocyte count is ≥ 200 cells per microliter, whichever occurs later [see Warnings and Precautions (5.9)]. 2.4 Preparation Instructions Follow the steps below to prepare the diluted solution of LEMTRADA for intravenous infusion: Inspect LEMTRADA visually for particulate matter and discoloration prior to administration. Do not use if particulate matter is present or the solution is discolored. Do not freeze or shake vials prior to use. Withdraw 1.2 mL of LEMTRADA from the vial into a syringe using aseptic technique and inject into a 100 mL bag of sterile 0.9% Sodium Chloride, USP or 5% Dextrose in Water, USP. 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 8 hours either at room temperature 15°C to 25°C (59°F to 77°F) or keep refrigerated at conditions 2°C to 8°C (36°F to 46°F). 2.5 Infusion Instructions Infuse LEMTRADA over 4 hours starting within 8 hours after dilution. Extend the duration of the infusion if clinically indicated. Administer LEMTRADA in a setting in which equipment and personnel to appropriately manage anaphylaxis or serious infusion reactions are available [see Warnings and Precautions (5.4)]. Do not add or simultaneously infuse other drug substances through the same intravenous line. Do not administer as an intravenous push or bolus. Monitor vital signs before the infusion and periodically during the infusion. Provide appropriate symptomatic treatment for infusion reactions as needed. Consider immediate discontinuation of the intravenous infusion if severe infusion reactions occur. Observe patients for infusion reactions during and for at least 2 hours after each LEMTRADA infusion. Consider longer periods of observation if clinically indicated. Inform patients that they should report symptoms that occur during and after each infusion because they may indicate a need for prompt medical intervention [see Warnings and Precautions (5.2)]. 2.6 Laboratory Testing and Monitoring to Assess Safety Conduct the following laboratory tests at baseline and at periodic intervals for 48 months following the last treatment course of LEMTRADA in order to monitor for early signs of potentially serious adverse effects: Complete blood count (CBC) with differential (prior to treatment initiation and at monthly 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 intervals thereafter) A test of thyroid function, such as thyroid stimulating hormone (TSH) level (prior to treatment initiation and every 3 months thereafter) Conduct baseline and yearly skin exams to monitor for melanoma [see Warnings and Precautions (5.3)].
Use in special populations
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm. (8.1) 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. LEMTRADA was embryolethal in pregnant huCD52 transgenic mice when administered during organogenesis. Auto-antibodies may develop after administration of LEMTRADA. Placental transfer of anti-thyroid antibodies resulting in neonatal Graves' disease has been reported. LEMTRADA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data When LEMTRADA was administered to pregnant huCD52 transgenic mice during organogenesis (gestation days [GD] 6-10 or GD 11-15) at doses of 3 or 10 mg/kg IV, no teratogenic effects were observed. However, there was an increase in embryolethality (increased post-implantation loss and the number of dams with all fetuses dead or resorbed) in pregnant animals dosed during GD 11-15. In a separate study in pregnant huCD52 transgenic mice, administration of LEMTRADA during organogenesis (GD 6-10 or GD 11-15) at doses of 3 or 10 mg/kg/IV, decreases in B lymphocytes and T-lymphocyte populations were observed in the offspring at both doses tested. The effects of LEMTRADA, administered during organogenesis, on postnatal development have not been adequately assessed. Clinical Considerations To avoid in utero exposure to LEMTRADA, women of child bearing potential should use effective contraceptive measures when receiving a course of treatment with LEMTRADA and for 4 months following that course of treatment. LEMTRADA induces persistent thyroid disorders [see Warnings and Precautions (5.7)]. Untreated hypothyroidism in pregnant women increases the risk for miscarriage and may have effects on the fetus including mental retardation and dwarfism. In mothers with Graves' disease, maternal thyroid stimulating hormone receptor antibodies can be transferred to a developing fetus and can cause neonatal Graves' disease. In a patient who developed Graves' disease after treatment with alemtuzumab, placental transfer of anti-thyrotropin receptor antibodies resulted in neonatal Graves' Disease with thyroid storm in her infant who was born 1 year after alemtuzumab dosing [see Warnings and Precautions (5.1)]. 8.3 Nursing Mothers Alemtuzumab was detected in the milk of lactating mice administered 10 mg/kg LEMTRADA on Days 8 through 12 postpartum. Serum levels of alemtuzumab were similar in lactating mice and offspring on Day 13 postpartum, and were associated with evidence of pharmacological activity (decrease in lymphocyte counts) in the offspring. It is not known whether alemtuzumab is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from LEMTRADA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness in pediatric patients less than 17 years of age have not been established. Use of LEMTRADA is not recommended in pediatric patients due to the risks of autoimmunity, infusion reactions, and because it may increase the risk of malignancies (thyroid, melanoma, lymphoproliferative disorders, and lymphoma) [see Warnings and Precautions (5.1, 5.2, 5.3)]. 8.5 Geriatric Use Clinical studies of LEMTRADA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
Pregnancy and lactation
8.3 Nursing Mothers Alemtuzumab was detected in the milk of lactating mice administered 10 mg/kg LEMTRADA on Days 8 through 12 postpartum. Serum levels of alemtuzumab were similar in lactating mice and offspring on Day 13 postpartum, and were associated with evidence of pharmacological activity (decrease in lymphocyte counts) in the offspring. It is not known whether alemtuzumab is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from LEMTRADA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

More information

Category Value
Authorisation number BLA103948
Agency product number 3A189DH42V
Orphan designation No
Product NDC 58468-0200
Date Last Revised 20-12-2017
Type HUMAN PRESCRIPTION DRUG
Storage and handling 16.2 Storage and Handling Store LEMTRADA vials at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Store in original carton to protect from light.
Marketing authorisation holder Genzyme Corporation
Warnings WARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES LEMTRADA causes serious, sometimes fatal, autoimmune conditions such as immune thrombocytopenia and anti-glomerular basement membrane disease. Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts at periodic intervals for 48 months after the last dose of LEMTRADA [see Warnings and Precautions (5.1)]. LEMTRADA causes serious and life threatening infusion reactions. LEMTRADA must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for two hours after each infusion. Make patients aware that serious infusion reactions can also occur after the 2-hour monitoring period [see Warnings and Precautions (5.2)]. LEMTRADA may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams [see Warnings and Precautions (5.3)]. Because of the risk of autoimmunity, infusion reactions, and malignancies, LEMTRADA is available only through restricted distribution under a Risk Evaluation Mitigation Strategy (REMS) Program. Call 1-855-676-6326 to enroll in the LEMTRADA REMS program [see Warnings and Precautions (5.4)]. WARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES See full prescribing information for complete boxed warning. LEMTRADA causes serious, sometimes fatal, autoimmune conditions such as immune thrombocytopenia and anti-glomerular basement membrane disease. Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine counts at periodic intervals for 48 months after the last dose. (5.1) LEMTRADA causes serious and life-threatening infusion reactions. LEMTRADA must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for two hours after each infusion. Make patients aware that serious infusion reactions can also occur after the 2-hour monitoring period. (5.2) LEMTRADA may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams. (5.3) LEMTRADA is available only through a restricted distribution program. (5.4)