Alemtuzumab

FDA Drug Information • Also known as: Campath, Lemtrada

Brand Names: Campath, Lemtrada
Drug Class: CD52-directed Cytolytic Antibody [EPC]
Route: INTRAVENOUS
Dosage Form: INJECTION, SOLUTION, CONCENTRATE
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: AUTOIMMUNITY, INFUSION REACTIONS, STROKE, 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 before starting treatment and then at monthly intervals until 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) ] . Serious and life-threatening stroke (including ischemic and hemorrhagic stroke) has been reported within 3 days of LEMTRADA administration. Instruct patients to seek immediate medical attention if symptoms of stroke occur [see Warnings and Precautions (5.3) ]. 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 (5.4) ] . 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 (5.5) ] . WARNING: AUTOIMMUNITY, INFUSION REACTIONS, STROKE, 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 cell counts monthly until 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 ) Serious and life-threatening stroke has been reported within 3 days of LEMTRADA administration. Instruct patients to seek immediate medical attention if symptoms of stroke occur. ( 5.3 ) LEMTRADA may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams. ( 5.4 ) LEMTRADA is available only through a restricted distribution program. ( 5.5 )

Description

11 DESCRIPTION Alemtuzumab is a recombinant humanized IgG1 kappa monoclonal antibody directed against the cell surface glycoprotein, CD52. Alemtuzumab has an approximate molecular weight of 150 kD. Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a nutrient medium containing neomycin. Neomycin is not detectable in the final product. LEMTRADA (alemtuzumab) injection is a sterile, clear and colorless to slightly yellow, solution (pH 7.2 ± 0.2) for intravenous infusion. Each 1 mL of solution contains 10 mg alemtuzumab, dibasic sodium phosphate (1.15 mg), disodium edetate dihydrate (0.0187 mg), polysorbate 80 (0.1 mg), potassium chloride (0.2 mg), potassium dihydrogen phosphate (0.2 mg), sodium chloride (8 mg), and Water for Injection, USP.

What Is Alemtuzumab Used For?

1 INDICATIONS AND USAGE LEMTRADA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. 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 [see Warnings and Precautions (5) ] . LEMTRADA is a CD52-directed cytolytic monoclonal antibody indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. 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. (1.5) Limitations of Use : LEMTRADA is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile. (1.5) Limitations of Use LEMTRADA is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile [see Warnings and Precautions (5) ].

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Baseline laboratory tests are required prior to treatment. ( 2.1 ) Administer LEMTRADA by intravenous infusion over 4 hours for 2 or more treatment courses: Initial treatment of 2 courses: First course: 12 mg/day on 5 consecutive days. ( 2.3 ) Second course: 12 mg/day on 3 consecutive days 12 months after first treatment course. ( 2.3 ) Subsequent treatment courses of 12 mg per day on 3 consecutive days (36 mg total dose) may be administered, as needed, at least 12 months after the last dose of any prior treatment course. ( 2.3 ) Premedicate with corticosteroids prior to LEMTRADA infusion for the first 3 days of each treatment course. ( 2.2 ) 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. ( 2.2 ) Must be diluted prior to administration. ( 2.4 ) 2.1 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 (5.15) ] : 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. 2.2 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 antiviral 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 at least 200 cells per microliter, whichever occurs later [see Warnings and Precautions (5.15) ] . 2.3 Recommended Dosage 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. Following the second treatment course, subsequent treatment courses of 12 mg per day on 3 consecutive days (36 mg total dose) may be administered, as needed, at least 12 months after the last dose of any prior treatment courses. 2.4 Preparation...

Side Effects (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) ] Stroke and Cervicocephalic Arterial Dissection [see Warnings and Precautions (5.3) ] Malignancies [see Warnings and Precautions (5.4) ] Immune Thrombocytopenia [see Warnings and Precautions (5.6) ] Glomerular Nephropathies Including Anti-glomerular Basement Membrane Disease [see Warnings and Precautions (5.7) ] Thyroid Disorders [see Warnings and Precautions (5.8) ] Other Autoimmune Cytopenias [see Warnings and Precautions (5.9) ] Autoimmune Hepatitis [see Warnings and Precautions (5.10) ] Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions (5.11) ] Adult Onset Still's Disease [see Warnings and Precautions (5.12) ] Thrombotic Thrombocytopenic Purpura (TTP) [see Warnings and Precautions (5.13) ] Autoimmune Encephalitis (AIE) [see Warnings and Precautions (5.14) ] Acquired Hemophilia A [see Warnings and Precautions (5.15) ] Immune-Mediated Colitis [see Warnings and Precautions (5.16) ] Infections [see Warnings and Precautions (5.17) ] Progressive Multifocal Leukoencephalopathy (PML) [see Warnings and Precautions (5.18) ] Acute Acalculous Cholecystitis [see Warnings and Precautions (5.19) ] Pneumonitis [see Warnings and Precautions (5.20) ] 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. The population was 18 to 55 years of age, 65% were female, and 92% were Caucasian. 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. In MS clinical studies (controlled and open-label extension), overall, a total of 1217 patients received LEMTRADA. Approximately 60% of patients received a total of 2 treatment courses and approximately 24% of patients received a total of 3 treatment courses; others received a total of 4 or more treatment courses, although data beyond 3 treatment courses are limited. The overall follow-up was 6858 person-years. Patients had a median of 6 years of follow-up from the first LEMTRADA dose, with approximately 14% having at least 7 years of follow-up. Most Common Adverse Reactions In controlled 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:...

Contraindications

4 CONTRAINDICATIONS LEMTRADA is contraindicated in patients: with known hypersensitivity or anaphylactic reactions to alemtuzumab or any of the excipients in LEMTRADA who are infected with human immunodeficiency virus (HIV) because LEMTRADA causes prolonged reductions of CD4+ lymphocyte counts with active infection Known hypersensitivity or anaphylactic reactions to alemtuzumab or any of the excipients in LEMTRADA ( 4 ) Infection with Human Immunodeficiency Virus ( 4 ) Active infection ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of LEMTRADA in pregnant women. LEMTRADA was embryolethal in pregnant huCD52 transgenic mice when administered during organogenesis [see Animal data ] . Auto-antibodies may develop after administration of LEMTRADA. Placental transfer of anti-thyroid antibodies resulting in neonatal Graves' disease has been reported. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. There is a pregnancy surveillance program for LEMTRADA. If LEMTRADA exposure occurs during pregnancy, healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2. Clinical Considerations LEMTRADA induces persistent thyroid disorders [see Warnings and Precautions (5.8) ] . 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) ] . Data 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 postimplantation loss and the number of dams with all fetuses dead or resorbed) in...

Overdosage

10 OVERDOSAGE Two MS patients experienced serious reactions (headache, rash, and either hypotension or sinus tachycardia) after a single accidental infusion up to 60 mg of LEMTRADA. Doses of LEMTRADA greater than those recommended may increase the intensity and/or duration of infusion reactions or its immune effects. There is no known antidote for alemtuzumab overdosage.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied LEMTRADA (alemtuzumab) injection is a sterile, clear and colorless to slightly yellow solution for intravenous infusion, containing no antimicrobial preservatives. Each LEMTRADA carton (NDC: 58468-0200-1) contains one single-dose vial that delivers 12 mg/1.2 mL (10 mg/mL). The vial stopper is not made with natural rubber latex. 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. 16.1 How Supplied LEMTRADA (alemtuzumab) injection is a sterile, clear and colorless to slightly yellow solution for intravenous infusion, containing no antimicrobial preservatives. Each LEMTRADA carton (NDC: 58468-0200-1) contains one single-dose vial that delivers 12 mg/1.2 mL (10 mg/mL). The vial stopper is not made with natural rubber latex.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.