Alemtuzumab

U.S. BRAND NAMES — Campath®
PHARMACOLOGIC CATEGORY Antineoplastic Agent, Monoclonal Antibody
DOSING: ADULTS B-CLL: I.V. infusion, SubQ (unlabeled route): Initial: 3 mg/day beginning on day 1; when tolerated, increase to 10 mg/day; when tolerated, increase to maintenance dose of 30 mg/day 3 times/week on alternate days for up to 12 weeks Maximum dose/day: 30 mg; maximum cumulative dose/week: 90 mg
Note: Dose escalation is required; usually accomplished in 3-7 days. Do not exceed single doses >30 mg or cumulative doses >90 mg/week. Pretreatment (with acetaminophen and an oral antihistamine) is recommended prior to the first dose, with dose escalations, and as clinically indicated; I.V. hydrocortisone may be used for severe infusion-related reactions.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [vial; preservative free]: Campath®: 30 mg/mL (1 mL) [contains polysorbate 80; disodium edetate dihydrate]
DOSAGE FORMS: CONCISE Injection, solution [vial; preservative free]: Campath®: 30 mg/mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer by I.V. infusion over 2 hours. Consider premedicating with diphenhydramine 50 mg and acetaminophen 650 mg 30 minutes before initiation of infusion. Hydrocortisone 200 mg has been effective in decreasing severe infusion-related events. Start anti-infective prophylaxis. Other drugs should not be added to or simultaneously infused through the same I.V. line. Do not give I.V. push.
SubQ (unlabeled route): A longer dose escalation time (1-2 weeks) may be needed due to injection site reactions. Pre-medication and anti-infective prophylaxis regimens should be given as are recommended with I.V. administration.
COMPATIBILITY — Medications should not be added to the solution or simultaneously infused through the same I.V. line.
USE — Treatment of B-cell chronic lymphocytic leukemia (B-CLL)
USE - UNLABELED / INVESTIGATIONAL — Treatment of refractory T-cell prolymphocytic leukemia (T-PLL); rheumatoid arthritis; graft-versus-host disease; multiple myeloma; preconditioning regimen for stem-cell transplantation and renal and liver transplantation; post-transplant rejection (renal); treatment of autoimmune cytopenias
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Hypotension (15% to 32%), peripheral edema (13%), hypertension (11% to 15%), tachycardia/SVT (11%) Central nervous system: Fever (83% to 85%), fatigue (22% to 34%), headache (13% to 24%), dysthesias (15%), dizziness (12%) Dermatologic: Rash (30% to 40%), urticaria (22% to 30%), pruritus (14% to 24%) Gastrointestinal: Nausea (47% to 54%), vomiting (33% to 41%), anorexia (20%), diarrhea (13% to 22%), stomatitis/mucositis (14%), abdominal pain (11%) Hematologic: Neutropenia (85%; grade 3/4: 64% to 70%; median duration: 28 days), anemia (80%; grade 3/4: 38% to 47%), thrombocytopenia (72%; grade 3/4: 50% to 52%; median duration: 21 days) Local: Injection site reaction (SubQ administration: 90%) Neuromuscular & skeletal: Rigors (86% to 89%), skeletal pain (24%), weakness (13%), myalgia (11%) Respiratory: Dyspnea (17% to 26%), cough (25%), bronchitis/pneumonitis (21%), pneumonia (16%), pharyngitis (12%) Miscellaneous: Infection (43% to 66%; grades 3/4: 37%; incidence is lower if prophylactic anti-infectives are utilized), diaphoresis (19%), sepsis (15%), herpes viral infections (1% to 11%)
1% to 10%: Cardiovascular: Chest pain (10%) Central nervous system: Insomnia (10%), malaise (9%), depression (7%), temperature change sensation (5%), somnolence (5%) Dermatologic: Purpura (8%) Gastrointestinal: Dyspepsia (10%), constipation (9%) Hematologic: Neutropenic fever (10%), pancytopenia/marrow hypoplasia (5% to 6%; grade 3/4: 3%), positive Coombs' test without hemolysis (2%), autoimmune thrombocytopenia (2%), autoimmune hemolytic anemia (1%) Neuromuscular & skeletal: Back pain (10%), tremor (7%) Respiratory: Bronchospasm (9%), epistaxis (7%), rhinitis (7%) Miscellaneous: Moniliasis (8%)
<1% (Limited to important or life-threatening): Abscess, acidosis, acute renal failure, acute respiratory distress syndrome, agranulocytosis, alkaline phosphatase increased, allergic reactions, anaphylactoid reactions, angina pectoris, angioedema, anuria, aphasia, arrhythmia, ascites, asthma, atrial fibrillation, bacterial infection, biliary pain, bone fracture, bone marrow aplasia, bronchitis, bullous eruption, capillary fragility, cardiac arrest, cardiac failure, cellulitis, cerebral hemorrhage, cerebrovascular disorder, coagulation abnormality, colitis, coma, confusion, COPD, coronary artery disorder, cyanosis, deep vein thrombosis, dehydration, diabetes mellitus exacerbation, disseminated intravascular coagulation (DIC), duodenal ulcer, endophthalmitis, esophagitis, facial edema, fluid overload, flu-like syndrome, gastroenteritis, gastrointestinal hemorrhage, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, hallucinations, haptoglobin decreased, hearing loss, hematemesis, hematoma, hematuria, hemolysis, hemolytic anemia, hemoptysis, hepatic failure, hepatocellular damage, hyperbilirubinemia, hyper-/hypoglycemia, hyper-/hypokalemia, hyperthyroidism, hypoalbuminemia, hyponatremia, hypovolemia, hypoxia, idiopathic thrombocytopenic purpura (ITP), interstitial pneumonitis, intestinal obstruction, intestinal perforation, intracranial hemorrhage, lymphadenopathy, lymphopenia, malignant lymphoma, marrow depression, melena, meningitis, MI, mouth edema, myositis, muscle atrophy, muscle weakness, optic neuropathy, osteomyelitis, otitis media, pancreatitis, paralysis, paralytic ileus, paroxysmal nocturnal hemoglobinuria-like monocytes, peptic ulcer, pericarditis, peritonitis, plasma cell dyscrasia, phlebitis, pleural effusion, pleurisy, Pneumocystis jiroveci pneumonia, pneumothorax, polymyositis, progressive multifocal leukoencephalopathy, pseudomembranous colitis, pulmonary edema, pulmonary embolism, pulmonary fibrosis, pulmonary infiltration, purpuric rash, renal dysfunction, respiratory alkalosis, respiratory arrest, respiratory depression, respiratory insufficiency, secondary leukemia, seizure (grand mal), serum sickness, splenic infarction, splenomegaly, stridor, subarachnoid hemorrhage, syncope, toxic nephropathy, transformation to aggressive lymphoma, transformation to prolymphocytic leukemia, thrombocythemia, thrombophlebitis, throat tightness, tuberculosis, tumor lysis syndrome, ureteric obstruction, urinary retention, urinary tract infection, ventricular arrhythmia, ventricular tachycardia, viral infection
CONTRAINDICATIONS — Known type 1 hypersensitivity or anaphylactic reaction to alemtuzumab or any component of the formulation; active systemic infections; underlying immunodeficiency (eg, seropositive for HIV)
WARNINGS / PRECAUTIONS Box warnings: Experienced physician: See "Other warnings/precautions" below. Hematologic toxicity: See "Concerns related to adverse effects" below. Infections: See "Concerns related to adverse effects" below. Infusion reactions: See "Concerns related to adverse effects" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Hematologic toxicity: [U.S. Boxed Warning]: Severe, prolonged myelosuppression, autoimmune anemia, and autoimmune thrombocytopenia have occurred. Single doses >30 mg and cumulative weekly doses >90 mg are associated with an increased incidence of pancytopenia and should not be administered. Median duration of neutropenia is 21 days; median duration of thrombocytopenia is 21 days. Discontinue therapy during serious hematologic or other serious toxicity until the event resolves. Permanently discontinue if autoimmune anemia or autoimmune thrombocytopenia occurs. Patients receiving blood products should only receive irradiated blood products due to the potential for GVHD during lymphopenia. Infections: [U.S. Boxed Warning]: Serious infections (bacterial, viral, fungal, and protozoan) have been reported. Prophylactic therapy against PCP pneumonia and herpes viral infections is recommended upon initiation of therapy and for at least 2 months following last dose or until CD4+ counts are 200 cells/µL. CD4+ and CD8+ lymphocyte counts may not return to baseline levels for more than 1 year. Withhold treatment during serious infections; may be reinitiated upon resolution of infection. Infusion reactions: [U.S. Boxed Warning]: Serious and potentially fatal infusion-related reactions (acute respiratory distress syndrome, bronchospasm, cardiac arrest, cardiac arrhythmias, chills, fever, hypotension, myocardial infarction, pulmonary infiltrates, rash, rigors, shortness of breath, syncope) may occur. Premedication with acetaminophen and an oral antihistamine is recommended. Use caution and carefully monitor blood pressure in patients with ischemic heart disease and patients on antihypertensive therapy. Gradual escalation to the recommended maintenance dose is required at initiation and after interruption of therapy for 7 days to minimize infusion-related reactions.
Special populations: Men of reproductive potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy. Pediatrics: Safety and efficacy have not been established in children. Women of childbearing potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Immunizations: Patients should not be immunized with live, viral vaccines during or recently after treatment. The ability to respond to any vaccine following therapy is unknown.
DRUG INTERACTIONS Monoclonal antibodies (eg, abciximab, infliximab, and rituximab): Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA antibodies.
Vaccine (dead organism): Alemtuzumab may decrease the effect of vaccines (dead organisms).
Vaccine (live organism): Alemtuzumab may enhance the adverse/toxic effects of vaccines (live organisms); vaccinal infections may develop.
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Echinacea may diminish the therapeutic effect of alemtuzumab.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Human IgG is known to cross the placental barrier; therefore, alemtuzumab may also cross the barrier and cause fetal B- and T-lymphocyte depletion. Well-controlled human trials have not been done. Use during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Effective contraception is recommended during and for 6 months after treatment for women of childbearing potential and men of reproductive potential.
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — Human IgG is excreted in breast milk; therefore, alemtuzumab may also be excreted in milk. Breast-feeding should be discontinued during treatment and for at least 3 months following the last dose.
MONITORING PARAMETERS — Vital signs; carefully monitor BP especially in patient with ischemic heart disease or on antihypertensive medications; CBC and platelets (weekly); signs and symptoms of infection; CD4+ lymphocyte counts (after treatment until recovery). Monitor closely for infusion reactions (including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash).
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms are likely to be extensions of adverse events (may include hematologic toxicity, respiratory distress, bronchospasm, anuria, tumor lysis syndrome). Single doses >30 mg or cumulative doses >90 mg/week have been associated with pancytopenia and severe (and occasionally fatal) ITP. Treatment is symptom-directed and supportive.
INTERNATIONAL BRAND NAMES — Campath (AR); MabCampath (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IL, IT, NL, NO, PL, PT, RU, SE, SG, TR)
MECHANISM OF ACTION — Binds to CD52, a nonmodulating antigen present on the surface of B and T lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. After binding to CD52+ cells, an antibody-dependent lysis of leukemic cells occurs.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 0.18 L/kg
Metabolism: Clearance decreases with repeated dosing (due to loss of CD52 receptors in periphery), resulting in a sevenfold increase in AUC.
Half-life elimination: 11 hours (following first 30 mg dose); 6 days (following the last 30 mg dose)
PATIENT INFORMATION — You will need frequent laboratory tests during course of therapy. Do not use any prescription or OTC medications unless approved by your prescriber. Maintain adequate hydration (2-3 L/day unless otherwise instructed) and nutrition (frequent small meals will help). You may experience abdominal pain, mouth sores, nausea, or vomiting (small frequent meals, good mouth care with soft toothbrush or swabs, sucking lozenges or chewing gum, and avoidance of spicy or salty foods may help). Report unresolved gastrointestinal problems, persistent fever, chills, muscle pain, skin rash, unusual bleeding or bruising, signs of infection (mouth sores, sore throat, white plaques in mouth or perianal area, burning on urination); swelling of extremities; difficulty breathing; chest pain or palpitations; or other persistent adverse reactions.
(For additional information see "Alemtuzumab: Patient drug information")