General: Simulect should be prescribed only by physicians who are experienced in the use of immunosuppressive therapy following organ transplantation.
Patients receiving Simulect should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources including medications for the treatment of severe hypersensitivity reactions.
Hypersensitivity reactions: Severe acute (less than 24 hours) hypersensitivity reactions have been observed both on initial exposure to Simulect and on re-exposure to a subsequent course of therapy. These included anaphylactoid type reactions such as urticaria, pruritus, sneezing, wheezing, hypotension, tachycardia, dyspnoea, bronchospasm, pulmonary oedema, cardiac failure, respiratory failure and capillary leak syndrome. If severe hypersensitivity occurs, therapy with Simulect should be permanently discontinued and no further dose should be administered. Caution should be exercised when patients previously given Simulect are re-exposed to a subsequent course of therapy with this medicine.
There is accumulating evidence that a subgroup of patients is at increased risk of developing hypersensitivity reactions. These are patients in whom, following the initial administration of Simulect, the concomitant immunosuppression was discontinued prematurely due, for example, to abandoned transplantation or early loss of the graft. Acute hypersensitivity reactions were observed on re-administration of Simulect for a subsequent transplantation in some of these patients.
Neoplasms and infections: Transplant patients receiving immunosuppressive regimens involving combinations with or without Simulect are at increased risk of developing lymphoproliferative disorders (LPDs) (such as lymphoma) and opportunistic infections (such as cytomegalovirus, CMV). In clinical trials, the incidence of opportunistic infections was similar in patients using immunosuppressive regimens with or without Simulect. In a pooled analysis of two five-year extension studies, no differences were found in the incidence of malignancies and LPDs between immunosuppressive regimens with or without Simulect (see ADVERSE REACTIONS).
Vaccination: No data are available on either the effects of live and inactive vaccination or the transmission of infection by live vaccines in patients receiving Simulect. Nevertheless, live vaccines are not recommended for immunosuppressed patients. Inactivated vaccines may be administered to immunosuppressed patients; however, response to the vaccine may depend on the degree of the immunosuppression.