WARNINGS AND PRECAUTIONS
Severe, including fatal, autoimmune anemia and thrombocytopenia, and prolonged myelosuppression have been reported in patients receiving Campath.
In addition, hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia have been reported after treatment with Campath at the recommended dose. Single doses of Campath greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia.
Withhold Campath for severe cytopenias (except lymphopenia). Discontinue for autoimmune cytopenias or recurrent/persistent severe cytopenias (except lymphopenia) [see DOSAGE AND ADMINISTRATION] . No data exist on the safety of Campath resumption in patients with autoimmune cytopenias or marrow aplasia [see ADVERSE REACTIONS] .
Adverse reactions occurring during or shortly after Campath infusion include pyrexia, chills/rigors, nausea, hypotension, urticaria, dyspnea, rash, emesis, and bronchospasm. In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. Monitor for the signs and symptoms listed above and withhold infusion for Grade 3 or 4 infusion reactions [see ADVERSE REACTIONS] .
The following serious, including fatal, infusion reactions have been identified in post-marketing reports: syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, cardiac arrhythmias, myocardial infarction, acute cardiac insufficiency, cardiac arrest, angioedema, and anaphylactoid shock.
Initiate Campath according to the recommended dose-escalation scheme [see DOSAGE AND ADMINISTRATION (2) ] . Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, meperidine) for infusion reactions as needed [ see DOSAGE AND ADMINISTRATION] . If therapy is interrupted for 7 or more days, reinstitute Campath with gradual dose escalation [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS (6) ] .
Campath treatment results in severe and prolonged lymphopenia with a concomitant increased incidence of opportunistic infections [see ADVERSE REACTIONS] . Administer PCP and herpes viral prophylaxis during Campath therapy and for a minimum of 2 months after completion of Campath or until the CD4+ count is ≥ 200 cells/µL, whichever occurs later [see DOSAGE AND ADMINISTRATION] . Prophylaxis does not eliminate these infections.
Routinely monitor patients for CMV infection during Campath treatment and for at least 2 months following completion of treatment. Withhold Campath for serious infections and during antiviral treatment for CMV infection or confirmed CMV viremia (defined as polymerase chain reaction (PCR) positive CMV in ≥ 2 consecutive samples obtained 1 week apart) [see ADVERSE REACTIONS] . Initiate therapeutic ganciclovir (or equivalent) for CMV infection or confirmed CMV viremia [see DOSAGE AND ADMINISTRATION] .
Administer only irradiated blood products to avoid transfusion associated Graft versus Host Disease (TAGVHD), unless emergent circumstances dictate immediate transfusion.1
In patients receiving Campath as initial therapy, recovery of CD4+ counts to ≥ 200 cells/µL occurred by 6 months post-treatment; however at 2 months post-treatment, the median was 183 cells/µL. In previously treated patients receiving Campath, the median time to recovery of CD4+ counts to ≥200 cells/µL was 2 months; however, full recovery (to baseline) of CD4+ and CD8+ counts may take more than 12 months [see BOXED WARNING and ADVERSE REACTIONS (6) ] .
Obtain complete blood counts (CBC) at weekly intervals during Campath therapy and more frequently if worsening anemia, neutropenia, or thrombocytopenia occurs. Assess CD4+ counts after treatment until recovery to ≥ 200 cells/µL [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS (6) ] .
The safety of immunization with live viral vaccines following Campath therapy has not been studied. Do not administer live viral vaccines to patients who have recently received Campath. The ability to generate an immune response to any vaccine following Campath therapy has not been studied.
USE IN SPECIFIC POPULATIONS
Pregnancy Category C
Animal reproduction studies have not been conducted with Campath. IgG antibodies, such as Campath, can cross the placental barrier. It is not known whether Campath can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Campath should be given to a pregnant woman only if clearly needed.
Excretion of Campath in human breast milk has not been studied; it is not known whether this drug is excreted in human milk. IgG antibodies, such as Campath, can be excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Campath, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the elimination half-life of Campath and the importance of the drug to the mother.
Safety and effectiveness have not been established in pediatric patients.
Of 147 previously untreated B-CLL patients treated with Campath, 35% were ≥ age 65 and 4% were ≥ age 75. Of 149 previously treated patients with B-CLL, 44% were ≥ 65 years of age and 10% were ≥ 75 years of age. Clinical studies of Campath did not include sufficient number of subjects age 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.