ALEMTUZUMAB

ALEMTUZUMAb (a-lem'tu-zu-mab) Campath Classifications: biologic response modifier; monocolonal antibody; antineoplastic; Therapeutic: antineoplastic; monoclonal antibody Prototype: Basiliximab Pregnancy Category: C

Availability

30 mg/mL injection

Action

Monoclonal antibody that attaches to CD52 cell surface antigens expressed on a variety of leukocytes, including normal and malignant B and T lymphocytes, monocytes, and some granulocytes. Proposed mechanism of action is antibody-dependent lysis of leukemic cells following binding to cell surface antigens.

Therapeutic Effect

Initiates antibody dependent cell lysis, thus inhibiting cell proliferation in chronic lymphocytic leukemia.

Uses

Treatment of B-cell chronic lymphocytic leukemia in patients who have failed fludarabine therapy.

Unlabeled Uses

Treatment of mycosis fungoides, non-Hodgkin's lymphoma.

Contraindications

Type I hypersensitivity to alemtuzumab or its components, hamster protein hypersensitivity; serious infection or exposure to viral infections (i.e., herpes or chickenpox), HIV infection, dental work; infection; pregnancy (category C), lactation.

Cautious Use

History of hypersensitivity to other monoclonal antibodies; ischemic cardiac disease, angina, coronary artery disease; dental disease; history of varicella disease; females of childbearing age. Safety and efficacy in children are not established.

Route & Dosage

B-Cell Chronic Lymphocytic Leukemia Adult: IV Start with 3 mg/d, when that is tolerated, increase dose over next 3–7 d to 10 mg/d; when 10 mg/d is tolerated, increase to maintenance dose of 30 mg/d (give 30 mg/d 3 times/wk). Single dose should not exceed 30 mg; cumulative dose should not exceed 90 mg/wk Toxicity Adjustment First time ANC falls below 250/mcL or platelet count falls below 25,000/mcL Stop therapy until ANC is at least 500 mcL and platelet count is at least 50,000 mcL, resume at previous dose If therapy is stopped for 7 or more days, re-start at 3 mg and taper up Second time ANC below 250/mcL or platelet count falls below 25,000 mcL Stop therapy until ANC is at least 500 mcL and platelet count is at least 50,000 mcL, resume at 10 mg dose If therapy is stopped for 7 or more days, re-start at 3 mg and taper up, do not exceed 10 mg Third time ANC below 250/mcL or platelet count falls below 25,000 mcL Stop therapy permanently *Patients starting therapy with baseline ANC <500 mcL or baseline platelet count <25,000 mcL who experience a 50% decrease from baseline should stop therapy until values return to baseline then resume at previous dose. If therapy is stopped for 7 or more days, re-start at 3 mg and taper up.

Administration

• Note: Premedication with antihistamines, acetaminophen, antiemetics, and corticosteroids prior to infusion may reduce the severity of adverse side effects.

Intravenous PREPARE: IV Infusion: Do NOT shake ampule prior to use. Withdraw required dose into a syringe with a sterile, low-protein binding, non-fiber releasing 5 micron filter. Inject into 100 mL NS or D5W. Gently invert bag to mix. Infuse within 8 h of mixing. Protect from light. Discard any unused solution. Use within 8 h of mixing.   ADMINISTER: IV Infusion: Infuse each dose over 2 h. Do NOT give single doses >30 mg or cumulative weekly doses >90 mg.   INCOMPATIBILITIES Solution/additive: Do not infuse or mix with other drugs.

• Store at 2°–8° C (36°–46° F). Discard if ampule has been frozen. Protect from direct light.

Adverse Effects (≥1%)

Body as a Whole: Infusion reactions (rigors, fever, nausea, vomiting, hypotension, rash, shortness of breath, bronchospasm, chills), fatigue, pain, sepsis, asthenia, edema, herpes simplex, myalgias, malaise, moniliasis, temperature change sensation, coma, seizures. CNS: Headache, dysesthesias, dizziness, insomnia, depression, tremor, somnolence, cerebrovascular accident, subarachnoid hemorrhage. CV: Hypotension, tachycardia, hypertension, cardiac failure, arrhythmias, MI. GI: Diarrhea, nausea, vomiting, stomatitis, abdominal pain, dyspepsia, anorexia, constipation. Hematologic: Neutropenia, anemia, thrombocytopenia, purpura, epistaxis, pancytopenia. Respiratory: Dyspnea, cough, bronchitis, pneumonia, pharyngitis, bronchospasm, rhinitis. Skin: Rash, urticaria, pruritus, increased sweating. Other: Risk of opportunistic infections.

Interactions

Drug: Additive risk of bleeding with anticoagulants, nsaids, platelet inhibitors, salicylates increased risk of opportunistic infections with fludarabine. Herbal: Feverfew, garlic, ginger, ginkgo may increase risk of bleeding.

Pharmacokinetics

Peak: Steady-state levels in approximately 6 wk. Half-Life: 12 d.

Nursing Implications

Assessment & Drug Effects

• Monitor for acute infusion-related events, including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash. If such a reaction occurs, the infusion should be discontinued and the physician notified.
• Withhold drug and notify physician if absolute neutrophil count <250/mcL or platelet count ≤25,000/mcL.
• Monitor BP closely during infusion period. Careful monitoring of BP and hypotensive symptoms is especially important in patients with ischemic heart disease and those on antihypertensives.
• Discontinue infusion and notify physician immediately if any of the following occurs: hypotension, fever, chills, shortness of breath, bronchospasm, or rash.
• Withhold drug during any serious infection. Therapy may be reinstituted following resolution of the infection.
• Lab tests: CBS with differential and platelet counts weekly or more frequently in the presence of anemia, thrombocytopenia, or neutropenia; periodic blood glucose, serum electrolytes, and alkaline phosphatase.
• Monitor diabetics closely for loss of glycemic control.
• Monitor for S&S of dehydration especially with severe vomiting.

Patient & Family Education

• Do not accept immunizations with live viral vaccines during therapy or if therapy has been recently terminated.
• Use effective methods of contraception to prevent pregnancy during therapy and for at least 6 mo following therapy.
• Report any of the following to physician immediately: unexplained bleeding, fever, sore throat, flu-like symptoms, S&S of an infection, difficulty breathing, significant GI distress, abdominal pain, fluid retention, or changes in mental status.
• Diabetics should monitor blood glucose levels carefully since loss of glycemic control is a possible adverse reaction.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug