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.

Recommended Premedication and Concomitant Medication

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.

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).

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, serious infusion reactions, myocardial ischemia, myocardial infarction, and cerebrovascular 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. Do not administer as an intravenous push or bolus.

Obtain a baseline ECG. 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)].

Laboratory Testing and Monitoring to Assess Safety

Measure the urine protein to creatinine ratio prior to initiation of treatment. Conduct the following laboratory tests at baseline and at periodic intervals until 48 months after 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)
• 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)].