Lemtrada

English name: LEMTRAD™ 9 (Lemtrad)

Chinese name: Alemtuzumab Injection

US initial approval: 2001

Indications

LEMTRADA is suitable for the treatment of patients with relapsing forms of multiple sclerosis (MS).

The use of MTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for MS treatment.

Dosage and Administration

1. Dosage Information

The recommended dose of LEMTRADA is 12 mg/day administered as an intravenous infusion for 2 treatment cycles:

Course 1: 12 mg/day on 5 consecutive days (total dose 60 mg)

Course 2: 12 mg/day on 3 consecutive days 12 months after the first course of treatment mg/day (total dose 36 mg).

2. Vaccinations

Patients should have completed any required immunizations at least 6 weeks before treatment with LEMTRADA [see Warnings and Precautions (5.9)].

Before treatment with LEMTRADA, determine whether the patient has had chickenpox or has been vaccinated against varicella-zoster virus (VZV). If not, test patients for VZV antibodies and consider vaccination if they are negative for antibodies. Defer treatment with LEMTRADA until 6 weeks after VZV vaccination.

3. Recommended Premedication and Concomitant Medications

Corticosteroids: Premedicate patients with a high-dose corticosteroid (1,000 mg methylprednisolone or equivalent) immediately before infusion of LEMTRADA and for the first 3 days of each course.

Herpes Prevention: Administer anti-viral prophylaxis against herpes virus infections, beginning on the first day of each treatment course and continuing for a minimum of two months after treatment with LEMTRADA or until the CD4+ lymphocyte count is ≥200 cells per microliter, whichever occurs first.

4. Preparation Instructions

Follow the following steps to prepare LEMTRADA as a dilute solution for intravenous infusion: Visually inspect LEMTRADA for particulate matter and discoloration before administration. Do not use if particulate matter is present or the solution is discolored.

Do not freeze or shake vial before use. To prepare, use aseptic technique to draw 1.2 mL of LEMTRADA from vial into a syringe and inject into a sterile 100 mL bag of 0.9% sodium chloride, USP, or 5% dextrose in water, USP. Gently invert the bag to mix the solution. Make sure the prepared solution is sterile as it does not contain antimicrobial preservatives. Each vial is single use. Protect diluted solutions from light and store either at room temperature 15°C to 25°C (59°F to 77°F) or in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 8 hours before administration.

5. Infusion instructions

Infuse LEMTRADA over 4 hours within 8 hours after dilution. Extend infusion time as clinically indicated. Do not give by intravenous push or bolus injection. Monitor vital signs before infusion and periodically during infusion. Treat as necessary to provide appropriate symptomatic management of infusion reactions. Observe patients for infusion reactions during and for at least 2 hours after each LEMTRADA infusion. Observe longer as clinically indicated.

Dosage forms and specifications

Injection: 12 mg/1.2 mL (10 mg/mL) in single-use vial. LEMTRADA is a clear and colorless to pale yellow solution that requires dilution before intravenous infusion.

Contraindications

Contraindications in patients infected with human immunodeficiency virus (HIV)

LEMTRADA Because LEMTRADA causes a prolonged decrease in CD4+ lymphocyte counts.

Warnings and Precautions

Autoimmunity

Treatment with LEMTRADA may result in the development of autoantibodies and an increased risk of severe autoimmune phase conditions. In clinical studies, LEMTRADA-treated patients experienced thyroid disease (34%), immune thrombocytopenia (2%), and glomerulonephropathy (0.3%).

Infusion Reactions

LEMTRADA causes cytokine release syndrome leading to infusion reactions, some of which may be serious and life-threatening. In clinical studies, 92% of patients treated with LEMTRADA experienced an infusion reaction.

Malignant Diseases

Thyroid Cancer: LEMTRADA may increase the risk of thyroid cancer.

Melanoma: LEMTRADA may increase the risk of melanoma. Lymphoproliferative disorders and lymphomas: Lymphoproliferative disorders and lymphomas have occurred in patients treated with MSLEMTRADA, including one case of post-treatment death of MALT lymphoma, Castleman disease, and non-Epstein Barr virus-associated Burkitt's lymphoma. Epstein Barr virus-associated lymphoproliferative disorders have been reported in postmarketing patients without MS.

Immune thrombocytopenia: Immune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients in MS clinical studies.

Glomerulonephropathy: Glomerulonephropathy occurred in 0.3% of LEMTRADA-treated patients in MS clinical trials.

Thyroid Disease: Autoimmune thyroid disease occurred in 34% of LEMTRADA-treated patients in clinical studies. Uncontrolled clinical studies followed for more than 7 years after the first LEMTRADA dose Other autoimmune cytopenias, infections, herpes virus infections, human papilloma virus, tuberculosis, fungal infections, listeria infections, hepatitis, pneumonia.

Drugs with the same active ingredient:

LEMTRADA contains the same active ingredient (alemtuzumab) as CAMPATH®. If LEMTRADA is considered for use in patients who have previously received CAMPATH, increased caution is required regarding immune system aggregation and prolonged continuation.

Adverse Reactions

The following serious adverse reactions are described in the following section and elsewhere in the labeling: autoimmunity, infusion reactions, immune thrombocytopenia, glomerulonephropathy, thyroid disease, other autoimmune cytopenias, infection, and pneumonia.

Most Common Adverse Reactions

In clinical trials, the most common adverse reactions with LEMTRADA (at least 10% of patients and more frequently than interferon beta-1a) were rash, headache, pyrexia, nasopharyngitis, Nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes virus infection, hives, itching, thyroid disease, fungal infection, arthritis, limb pain, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.

Use in Special Populations

Pregnancy

There are no appropriate and well-controlled studies in pregnant women. To avoid in utero exposure to LEMTRADA, women of childbearing potential should use effective contraception while receiving a course of treatment with LEMTRADA and for 4 months following a course of treatment.

Breastfeeding mothers

It is unknown whether alemtuzumab is excreted in human milk. Because many drugs are excreted in breast milk, and because of the potential for serious adverse reactions in nursing infants from LEMTRADA, the decision whether to continue breastfeeding or discontinue the drug should be made, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in children younger than 17 years of age have not been established. LEMTRADA is not recommended for use in pediatric patients due to autoimmunity, infusion reactions, and because of a possible increased risk of malignant disease (thyroid, melanoma, lymphoproliferative disorders, and lymphoma).

Geriatric use

Clinical studies of LEMTRADA did not include sufficient numbers of patients aged 65 and older to determine whether they responded differently than younger patients.

Overdose

Two patients with MS experienced severe reactions (headache, rash, and/or hypotension or sinus tachycardia) after a single accidental infusion of 60 mg of LEMTRADA. Doses of LEMTRADA greater than recommended may increase the magnitude or duration of infusion reactions or their immunological effects. There is no known antidote for alemtuzumab overdose.

Storage and Disposal

Store LEMTRADA vials at 2°C to 8°C (36°F to 46°F).

Do not freeze or shake. Store in original carton away from light.