Campath Warnings, Precautions, Pregnancy, Nursing, Abuse - Alemtuzumab

Campath Warnings, Precautions, Pregnancy, Nursing, Abuse - Alemtuzumab

WARNINGS

Campath has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bronchospasm, chills,and/or rash. In order to ameliorate or avoid infusion-related events, patients should be premedicated with an oral antihistamine and acetaminophen prior to dosing and monitored closely for infusion-related adverse events. In addition, Campath should be initiated at a low dose with gradual escalation to the effective dose. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive medications. If therapy is interrupted for 7 or more days, Campath should be reinstituted with gradual dose escalation.(See ADVERSE EVENTS and DOSAGE AND ADMINISTRATION.)

Campath induces profound lymphopenia. A variety of opportunistic infections have been reported in patients receiving Campath therapy (see ADVERSE EVENTS, Infections). If a serious infection occurs, Campath therapy should be interrupted and may be reinitiated following the resolution of the infection.

Anti-infective prophylaxis is recommended upon initiation of therapy and for a minimum of 2 months following the last dose of Campath or until CD4⁺ counts are ³ 200 cells/mL. The median time to recovery of CD4⁺ counts to ³200/mL was 2 months, however, full recovery (to baseline) of CD4⁺ and CD8⁺ counts may take more than 12 months.(See BOXED WARNING and DOSAGE AND ADMINISTRATION.)

Because of the potential for Graft versus Host Disease (GVHD) in severely lymphopenic patients, irradiation of any blood products administered prior to recovery from lymphopenia is recommended.

Severe,prolonged, and in rare instances fatal, myelosuppression has occurred in patients with leukemia and lymphoma receiving Campath. Bone marrow aplasia and hypoplasia were observed in the clinical studies at the recommended dose. The incidence of these complications increased with doses above the recommended dose. In addition, severe and fatal autoimmune anemia and thrombocytopenia were observed in patients with CLL. Campath should be discontinued for severe hematologic toxicity (see Table 3 Dose Modification and Reinitiation of Therapy for Hematologic Toxicity) or in any patient with evidence of autoimmune hematologic toxicity. Following resolution of transient, non-immune myelosuppression, Campath may be reinitiated with caution.(See DOSAGE AND ADMINISTRATION.) There is no information on the safety of resumption of Campath in patients with autoimmune cytopenias or marrow aplasia.(See ADVERSE REACTIONS.)

Complete blood counts (CBC) and platelet counts should be obtained at weekly intervals during Campath therapy and more frequently if worsening anemia, neutropenia, or thrombocytopenia is observed on therapy.CD4⁺ counts should be assessed after treatment until recovery to ³200 cells/mL.(See WARNINGS and ADVERSE REACTIONS.)

No formal drug interaction studies have been performed with Campath. An immune response to Campath may interfere with subsequent diagnostic serum tests that utilize antibodies.

Patients who have recently received Campath, should not be immunized with live viral vaccines, due to their immunosuppression. The safety of immunization with live viral vaccines following Campath therapy has not been studied. The ability to generate a primary or anamnestic humoral response to any vaccine following Campath therapy has not been studied.

Four (1.9%) of 211 patients evaluated for development of an immune response were found to have antibodies to Campath. The data reflect the percentage of patients whose test results were considered positive for antibody to Campath in a kinetic enzyme immunoassay, and are highly dependent on the sensitivity and specificity of the assay. The observed incidence of antibody positivity may be influenced by several additional factors including sample handling, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Campath with the incidence of antibodies to other products may be misleading. Patients who develop hypersensitivity to Campath may have allergic or hypersensitivity reactions to other monoclonal antibodies.

No long-term studies in animals have been performed to establish the carcinogenic or mutagenic potential of Campath, or to determine its effects on fertility in males or females. Women of childbearing potential and men of reproductive potential should use effective contraceptive methods during treatment and for a minimum of 6 months following Campath therapy.

Pregnancy Category C: Animal reproduction studies have not been conducted with Campath.It is not known whether Campath can affect reproductive capacity or cause fetal harm when administered to a pregnant woman. However, human IgG is known to cross the placental barrier and therefore Campath may cross the placental barrier and cause fetal B and T lymphocyte depletion. Campath should be given to a pregnant woman only if clearly needed.

Excretion of Campath in human breast milk has not been studied. Because many drugs including human IgG are excreted in human milk, breast-feeding should be discontinued during treatment and for at least 3 months following the last dose of Campath.

The safety and effectiveness of Campath in children have not been established.

Of the 149 patients with B-CLL enrolled in the three clinical studies,66 (44%) were 65 and over, while 15 (10%) were 75 and over. Substantial differences in safety and efficacy related to age were not observed; however the size of the database is not sufficient to exclude important differences.