Usual Adult Dose for Multiple Sclerosis

LEMTRADA(R) 10 mg/mL:

• First treatment course: 12 mg IV over 4 hours daily for 5 consecutive days
• Second treatment course: 12 mg IV over 4 hours daily for 3 consecutive days administered 12 months after the first treatment course
• Maintenance dose: 12 mg IV over 4 hours daily for 3 consecutive days may be administered, if needed, at least 12 months after the last dose of the prior treatment course

Comments:

• Note: Consult manufacturer product information for approved indications. Different products have different approved indications.
• Complete necessary immunizations at least 6 weeks prior to treatment.
• Determine if patients have a history of varicella or have been vaccinated for varicella zoster virus (VZV); if not, test for antibodies to VZV and consider vaccination for those who are antibody-negative. Postpone treatment with this drug until 6 weeks after VZV vaccination.
• Perform tuberculosis (TB) screening according to local guidelines.
• Instruct patients to avoid potential sources of Listeria monocytogenes.
• Premedicate patients with high dose corticosteroids (1000 mg methylprednisolone or equivalent) immediately prior to infusion and for the first 3 days of each course.
• Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of 2 months following treatment discontinuation or until the CD4+ lymphocyte count is at least 200 cells per microliter, whichever occurs later.

Use: For relapsing forms of multiple sclerosis (MS) including relapsing-remitting disease and active secondary progressive disease; because of its safety profile, use should be reserved for patients who have had an inadequate response to 2 or more drugs for MS; not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile

Usual Adult Dose for Chronic Lymphocytic Leukemia

CAMPATH (R) 30 mg/mL:
Escalate dosing over 3 to 7 days at initiation of treatment or if dosing is held 7 days or more:
ESCALATION STRATEGY: 3 mg IV over 2 hours daily until infusion reactions are Grade 2 or less, then 10 mg IV over 2 hours daily until infusion reactions are Grade 2 or less, then 30 mg/day IV over 2 hours 3 times a week on alternate days (e.g., Mon/Wed/Fri).
Duration of therapy: 12 weeks (including dose escalation)

Comments:

• Note: Consult manufacturer product information for approved indications. Different products have different approved indications.
• Single doses of greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia.
• Premedicate with diphenhydramine (50 mg) and acetaminophen (500 to 1000 mg) 30 minutes prior to first infusion and each dose escalation.
• Institute medical management (e.g., steroids, epinephrine, meperidine) for infusion reactions.
• Administer trimethoprim/sulfamethoxazole DS (or equivalent) orally 2 times a day 3 times a week as Pneumocystis jiroveci pneumonia (PCP) prophylaxis.
• Administer famciclovir 250 mg orally 2 times a day (or equivalent) as herpetic prophylaxis.
• Continue PCP and herpes viral prophylaxis for a minimum of 2 months after completion of treatment or until the CD4+ count is 200 cells/microliter or greater, whichever occurs later.

Use: As a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL)

Usual Pediatric Dose for Multiple Sclerosis

17 years and older:
LEMTRADA(R) 10 mg/mL:

• First treatment course: 12 mg IV over 4 hours daily for 5 consecutive days
• Second treatment course: 12 mg IV over 4 hours daily for 3 consecutive days administered 12 months after the first treatment course
• Maintenance dose: 12 mg IV over 4 hours daily for 3 consecutive days may be administered, if needed, at least 12 months after the last dose of the prior treatment course

Comments:

• Note: Consult manufacturer product information for approved indications. Different products have different approved indications.
• Complete necessary immunizations at least 6 weeks prior to treatment.
• Determine if patients have a history of varicella or have been vaccinated for varicella zoster virus (VZV); if not, test for antibodies to VZV and consider vaccination for those who are antibody-negative. Postpone treatment with this drug until 6 weeks after VZV vaccination.
• Perform tuberculosis (TB) screening according to local guidelines.
• Instruct patients to avoid potential sources of Listeria monocytogenes.
• Premedicate patients with high dose corticosteroids (1000 mg methylprednisolone or equivalent) immediately prior to infusion and for the first 3 days of each course.
• Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of 2 months following treatment discontinuation or until the CD4+ lymphocyte count is at least 200 cells per microliter, whichever occurs later.

Use: For relapsing forms of multiple sclerosis (MS) including relapsing-remitting disease and active secondary progressive disease; because of its safety profile, use should be reserved for patients who have had an inadequate response to 2 or more drugs for MS; not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

CAMPATH (R):
DOSE MODIFICATIONS FOR B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA (B-CLL):

• Withhold therapy during serious infection or other serious adverse reactions until resolution.
• Discontinue therapy for autoimmune anemia or autoimmune thrombocytopenia.
• There are no dose modifications recommended for lymphopenia.

DOSE MODIFICATION FOR NEUTROPENIA OR THROMBOCYTOPENIA:
ANC LESS THAN 250 PER MICROLITER AND/OR PLATELET COUNT LESS THAN OR EQUAL TO 25,000 PER MICROLITER:

• FIRST OCCURRENCE: Withhold therapy; resume at 30 mg when ANC is greater than or equal to 500 per microliter and platelet count is greater than or equal to 50,000 per microliter.
• SECOND OCCURRENCE: Withhold therapy; resume at 10 mg when ANC is greater than or equal to 500 per microliter and platelet count is greater than or equal to 50,000 per microliter.
• THIRD OCCURRENCE: Discontinue therapy.

GREATER THAN OR EQUAL TO 50% DECREASE FROM BASELINE IN PATIENTS INITIATING THERAPY WITH A BASELINE ANC LESS THAN OR EQUAL TO 250 PER MICROLITER AND/OR A BASELINE PLATELET COUNT LESS THAN OR EQUAL TO 25,000 PER MICROLITER:

• FIRST OCCURRENCE: Withhold therapy; resume at 30 mg upon return to baseline.
• SECOND OCCURRENCE: Withhold therapy; resume at 10 mg upon return to baseline.
• THIRD OCCURRENCE: Discontinue therapy.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Lemtrada (R). It includes a communication plan, elements to assure safe use, and an implementation system. For additional information: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
LEMTRADA (R):

• This drug causes serious, sometimes fatal, autoimmune conditions (e.g., immune thrombocytopenia, anti-glomerular basement membrane disease). Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts at periodic intervals during and for 48 months after treatment is discontinued.
• This drug causes serious and life-threatening infusion reactions. Administer in a setting with equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for 2 hours after each infusion. Inform patients that serious infusion reactions can also occur after the 2-hour monitoring period.
• Serious and life-threatening stroke (e.g., ischemic stroke, hemorrhagic stroke) has been reported within 3 days of administering this drug. Instruct patients to seek immediate medical attention if symptoms of stroke occur.
• This drug may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams.
• Because of the risk of autoimmunity, infusion reactions, and malignancies, this drug 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.

CAMPATH (R):

• Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur. Single doses greater than 30 mg or cumulative doses greater than 90 mg per week increase the risk.
• Infusion Reactions: This drug can cause serious, including fatal, infusion reactions. Monitor patients during infusions and withhold treatment for Grade 3 or 4 infusion reactions. Gradually escalate to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days.
• Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections have been reported. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections,

CONTRAINDICATIONS:
LEMTRADA (R):

• In patients who are infected with Human Immunodeficiency Virus (HIV-None) because it causes prolonged reductions of CD4+ lymphocyte counts

CAMPATH (R):

• None

• Safety and efficacy of Lemtrada (R) have not been established in patients younger than 17 years.
• Safety and efficacy of Campath (R) have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Do not administer as an IV push or bolus.

General:

• Manufacturer product information should be consulted. Different trade names have separate indications, dosing, storage, and reconstitution requirements.
• Specialists and equipment required for the timely diagnosis and management of serious adverse reactions, especially autoimmune conditions and infections, should be available.

Monitoring:
CARDIOVASCULAR:

• Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease, angina, and/or in patients receiving antihypertensive medication.
• Assessment and ongoing monitoring of cardiac function is recommended in patients previously treated with potentially cardiotoxic agents.

HEMATOLOGIC:

• Baseline full blood counts and platelet counts, repeated at regular intervals during therapy and more frequently in patients that develop cytopenias.

Patient advice:

• Patients should be given the Package Leaflet, the Patient Alert Card and the Patient Guide.
• Before treatment, patients should be informed about the risks and benefits, and the need to commit to 48-months of follow-up after the last infusion.

Frequently asked questions

• What are the new drugs used for multiple sclerosis (MS)?