Safety Profile

Management of cytopenias

Severe, including fatal, autoimmune anemia and thrombocytopenia, and prolonged myelosuppression have been reported in patients receiving Campath.

Cytopenias (grade 3/4)

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 (2.3)]. No data exist on the safety of Campath resumption in patients with autoimmune cytopenias or marrow aplasia [see ADVERSE REACTIONS (6.1)].

Management of infusion 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 signs and symptoms and withhold infusion for grade 3 or 4 infusion reactions [see ADVERSE REACTIONS (6.1)].

The following serious, including fatal, infusion reactions have been identified in postmarketing reports: syncope, pulmonary infiltrates, acute respiratory distress syndrome, 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 (eg, glucocorticoids, epinephrine, meperidine) for infusion reactions as needed [see DOSAGE AND ADMINISTRATION (2.2)]. If therapy is interrupted for 7 or more days, reinstitute Campath with gradual dose escalation [see DOSAGE AND ADMINISTRATION (2.3) and ADVERSE REACTIONS (6)].

Management of infections

Campath treatment results in severe and prolonged lymphopenia with a concomitant increased incidence of opportunistic infections [see ADVERSE REACTIONS (6.1)].

Infections (all grades)

*Total infections exclude patients with any CMV events.

†CMV viremia (without evidence of symptoms) includes both cases of single polymerase chain reaction (PCR)-positive test results and of confirmed CMV viremia ( 2 occasions in consecutive samples 1 week apart). For the latter, ganciclovir (or equivalent) was initiated per protocol.

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 (2.2)]. Prophylaxis does not eliminate these infections.

Routinely monitor patients for cytomegalovirus (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 positive [PCR] CMV in ≥2 consecutive samples obtained 1 week apart) [see ADVERSE REACTIONS (6.1)]. Initiate therapeutic ganciclovir (or equivalent) for CMV infection or confirmed CMV viremia [see DOSAGE AND ADMINISTRATION (2.3)].

Administer only irradiated blood products to severely lymphopenic patients to avoid graft versus host disease (GVHD) unless emergent circumstances dictate immediate transfusion.

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)].

Laboratory monitoring

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 (5.3) and ADVERSE REACTIONS (6)].

Immunization

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.

Patient counseling information

Cytopenias: Advise patients to report any signs or symptoms such as bleeding, easy bruising, petechiae or purpura, pallor, weakness or fatigue [see WARNINGS AND PRECAUTIONS (5.1) and ADVERSE REACTIONS (6.1)].

Infusion Reactions: Advise patients of the signs and symptoms of infusion reactions and of the need to take premedications as prescribed [see WARNINGS AND PRECAUTIONS, (5.2) and OVERALL ADVERSE REACTIONS (6.1)].

Infections: Advise patients to immediately report symptoms of infection (eg, pyrexia) and to take prophylactic anti-infectives for PCP (trimethoprim/sulfamethoxazole DS or equivalent) and for herpes virus (famciclovir or equivalent) as prescribed [see WARNINGS AND PRECAUTIONS, (5.3) and ADVERSE REACTIONS (6.1)].

Advise patients that irradiation of blood products is required until adequate lymphocyte recovery [see WARNINGS AND PRECAUTIONS (5.3)].

Advise patients that they should not be immunized with live viral vaccines if they have recently been treated with Campath [see WARNINGS AND PRECAUTIONS (5.5)].

Advise male and female patients with reproductive potential to use effective contraceptive methods during treatment and for a minimum of 6 months following Campath therapy [see NONCLINICAL TOXICOLOGY (13.1)].