Class: Monoclonal antibody
- Solution for injection (concentrate) 30 mg/mL
Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody. Alemtuzumab binds to CD52, a nonmodulating antigen that is present on the surface of essentially all B- and T-lymphocytes, a majority of monocyte, macrophages, NK cells, and a subpopulation of granulocytes. The proposed mechanism of action is antibody-dependent lysis of leukemic cells following cell surface binding.
Vd at steady state is about 0.18 L/kg.
Displays nonlinear elimination kinetics. Systemic Cl decreases with repeated administration because of decreased receptor-mediated Cl (loss of CD52 receptors in the periphery). Mean t ½ was 11 h after first dose and 6 days after 12 wk of therapy.
Indications and Usage
Treatment of B-cell chronic lymphocytic leukemia.
Treatment of rheumatoid arthritis; multiple sclerosis.
Dosage and AdministrationB-Cell Chronic Lymphocytic Leukemia
IV Administer as an IV infusion over 2 h. Escalation to a maximum recommended dose of 30 mg is required at initiation of dosing or if dosing is withheld for 7 days or more. Escalation to 30 mg ordinarily can be achieved in 3 to 7 days. Start with 3 mg daily until infusion reactions are grade 2 or less. Then administer 10 mg daily until infusion reactions are grade 2 or less. Then administer 30 mg/day 3 times/wk on alternate days (eg, Monday-Wednesday-Friday). The total duration of therapy, including dose escalation, is 12 weeks.Recommended Concomitant Medications
Premedicate with diphenhydramine 50 mg and acetaminophen 500 to 1,000 mg 30 minutes prior to first infusion and each dose escalation. Also administer Pneumocystis jiroveci pneumonia (PCP) prophylaxis with trimethoprim/sulfamethoxazole double-strength twice daily 3 times/wk. Administer famciclovir 250 mg twice daily or equivalent as herpetic prophylaxis. Continue PCP and herpes viral prophylaxis for at least 2 mo after completion of alemtuzumab or until the CD4+ count is at least 200 cells/mcL, whichever occurs later.Dose Adjustment
IV Withhold alemtuzumab during serious infection or other serious adverse reactions until resolution. Discontinue alemtuzumab if autoimmune anemia or autoimmune thrombocytopenia occurs. There are no dose modifications recommended for lymphopenia.Dosage Adjustment for Neutropenia or Thrombocytopenia (patients with a baseline absolute neutrophil count [ANC] less than 250/mcL and/or a platelet count of 25,000/mcL or less)
IV If delay between dosing is less than 7 days, resume therapy at same dose. If delay is 7 days or more, resume therapy at 3 mg, increasing to 10 mg and then 30 mg as tolerated. First occurrence: Withhold alemtuzumab therapy; resume at 30 mg when ANC is at least 500/mcL and platelet count is at least 50,000/mcL. Second occurrence: Withhold alemtuzumab; resume at 10 mg when ANC is at least 500/mcL and platelet count is at least 50,000/mcL. Third occurrence: Discontinue alemtuzumab therapy.Dosage Adjustment for Neutropenia or Thrombocytopenia (at least a 50% decrease from baseline in patients initiating therapy with a baseline ANC of 250/mcL or less and/or a baseline platelet count of 25,000/mcL or less)
IV If the delay between dosing is less than 7 days, resume therapy at same dose. If delay is 7 days or more, resume therapy at 3 mg, increasing to 10 mg and then 30 mg as tolerated. First occurrence: Withhold alemtuzumab therapy; resume at 30 mg upon return to baseline values. Second occurrence: Withhold alemtuzumab; resume at 10 mg upon return to baseline values. Third occurrence: Discontinue alemtuzumab therapy.
- For IV infusion only. Not for intradermal, subcutaneous, IM, IV push or bolus, or intra-arterial administration. Do not shake vial prior to use.
- Withdraw necessary amount of alemtuzumab from vial into syringe (0.1 mL for 3 mg dose; 0.33 mL for 10 mg dose; 1 mL for 30 mg dose) and inject into 100 mL sterile sodium chloride 0.9% or dextrose 5% in water. Gently invert bag to mix solution.
- Administer infusion solution within 8 h after dilution.
- Administer infusion solution over a 2-h period.
- If infusion-related reaction occurs, treat with appropriate medical management (eg, steroids, epinephrine, meperidine).
- Do not add or simultaneously infuse other drug substances through same IV line.
- Do not use if solution is discolored, cloudy, or contains particulate matter.
- Discard any unused solution. Do not save unused solution for future use.
Store vials in refrigerator (36° to 46°F). Protect from direct sunlight and freezing. Discard if vial has been frozen. Diluted infusion solution may be stored for up to 8 h at controlled room temperature (59° to 86°F) or refrigerated (36° to 46°F). Protect from light.
None well documented.
Laboratory Test Interactions
None well documented.
Hypotension (16%); hypertension (14%); tachycardia (10%); cardiomyopathy, decreased injection fraction (postmarketing).
Pyrexia (69%); headache (14%); insomnia (10%); anxiety (8%); anorexia, dysesthesia, fatigue (more than 5%); tremor (3%).
Urticaria (16%); rash (13%); erythema (4%).
Optic neuropathy (postmarketing).
Diarrhea (10%); emesis, mucositis, nausea (more than 5%); abdominal pain.
Lymphopenia (97%); neutropenia (77%); anemia (76%); thrombocytopenia (71%); aplastic anemia (postmarketing).
Tumor lysis syndrome (postmarketing).
Musculoskeletal pain (more than 5%).
Dyspnea (14%); bronchospasm (more than 5%).
Cytomegalovirus (CMV) viremia (55%); chills (53%); CMV infection (16%); immunosuppression/infections; infusion reactions (including chills, dyspnea, hypotension, nausea, pyrexia, rash, tachycardia, urticaria); chronic inflammatory demyelinating polyradiculoneuropathy, Epstein-Barr virus, fatal infusion reactions, Goodpasture syndrome, Graves disease, Guillain-Barré syndrome, progressive multifocal leukoencephalopathy, serum sickness (postmarketing).
Alemtuzumab has been associated with infusion-related reactions, including fatal infusion reactions. Initiate alemtuzumab at a low dose with gradual escalation to the effective dose. Carefully monitor patients during infusions.
Serious, potentially fatal pancytopenia, marrow hypoplasia, idiopathic thrombocytopenia, and autoimmune hemolytic anemia have occurred.
Serious, sometimes fatal, opportunistic infections (bacterial, viral, fungal, protozoan) have been reported.
Routinely monitor patients for CMV infection during treatment and for at least 2 months following completion of treatment. Obtain CBC and platelet counts at weekly intervals during therapy and more frequently if worsening anemia, neutropenia, or thrombocytopenia is noted. Assess CD4 counts after treatment until recovery to at least 200 cells/mcL.
Category C .
Safety and efficacy not established.
Clinical studies did not include enough subjects 65 years of age and older to determine whether they respond differently than younger subjects.
Discontinue further therapy if the patient experiences anaphylaxis. Patients who are hypersensitive to alemtuzumab may react to other monoclonal antibodies.
Use additional caution in patients with ischemic heart disease or patients receiving antihypertensive medications.
Do not immunize patients who recently received alemtuzumab with live viral vaccines.
Alemtuzumab may cause profound immunosuppression and increased risk of infection during treatment and up to 12 mo afterward.
Patients with profound lymphopenia are at risk for graft-vs-host disease when nonirradiated blood products are given. Administration of irradiated blood products is recommended.
To minimize risks of serious opportunistic infections, give anti-infective prophylaxis during and for 2 mo after completion of alemtuzumab therapy, or until CD4 count is at least 200 cells/mcL, whichever occurs later.
Anuria, bone marrow aplasia, bronchospasm, cough, death, dyspnea, infections, severe infusion reactions.
- Advise patient or caregiver that alemtuzumab will be prepared and administered by health care provider in a health care setting.
- Advise patient that additional medications to prevent infections and infusion-related reactions may be ordered and to take exactly as prescribed.
- Advise family or caregiver to report any of the following to health care provider: any sign of infection; bleeding or unusual bruising; changes in heart rhythm; chest pain; chills; diarrhea; fainting; fever; hives; itching; mouth sores; persistent nausea; rash; sore throat; unexplained shortness of breath or difficulty breathing; vomiting; or any other unusual or unexplained symptoms.
- Advise patient that medication may cause drowsiness or dizziness and not to drive or perform other activities requiring mental alertness or coordination until tolerance is determined.
- Caution patient not to receive live viral vaccines during treatment with alemtuzumab or within several months after completing therapy.
- Advise women of childbearing potential and men of reproductive potential to use effective contraception during and for at least 6 mo following treatment.
- Instruct women not to breast-feed during treatment and for at least 3 mo following the last dose of alemtuzumab.
Copyright © 2009 Wolters Kluwer Health.
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