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. The use of live attenuated vaccines should therefore be avoided in patients treated with Simulect. Inactivated vaccines may be administered to immunosuppressed patients; however, response to the vaccine may depend on the degree of the immunosuppression, therefore vaccination during treatment with Simulect may be less effective.

 

Use in heart transplantation 

 

The efficacy and safety of Simulect for the prophylaxis of acute rejection in recipients of solid organ allografts other than renal have not been demonstrated. In several small clinical trials in heart transplant recipients, serious cardiac adverse events such as cardiac arrest (2.2%), atrial flutter (1.9%) and palpitations (1.4%) have been reported more frequently with Simulect than with other induction agents.

 

4.5 Interaction with other medicinal products and other forms of interaction

 

Because basiliximab is an immunoglobulin, no metabolic drug-drug interactions are to be expected.

 

In addition to ciclosporin for microemulsion, steroids, azathioprine and mycophenolate mofetil, other concomitant medications routinely administered in organ transplantation have been administered in clinical trials without any incremental adverse reactions. These concomitant medications include systemic antiviral, antibacterial and antimycotic medications, analgesics, antihypertensive medications such as beta-blocking agents or calcium channel blockers, and diuretics.

 

Human antimurine antibody (HAMA) responses were reported in a clinical trial of 172 patients treated with basiliximab, without predictive value for clinical tolerability. The incidence was 2/138 in patients not exposed to muromonab-CD3 (OKT3) and 4/34 in patients who received muromonab-CD3 concomitantly. The use of basiliximab does not preclude subsequent treatment with murine antilymphocyte antibody preparations.

 

In the original phase III studies during the first 3 months post-transplantation, 14% of patients in the basiliximab group and 27% of patients in the placebo group had an acute rejection episode treated with antibody therapy (OKT 3 or antithymocyte globulin/antilymphocyte globulin [ATG/ALG]), with no increase in adverse events or infections in the basiliximab group as compared to placebo.

 

Three clinical trials have investigated basiliximab use in combination with a triple therapy regimen which included either azathioprine or mycophenolate mofetil. The total body clearance of basiliximab was reduced by an average 22% when azathioprine was added to a regimen consisting of ciclosporin for microemulsion and corticosteroids. The total body clearance of basiliximab was reduced by an average 51% when mycophenolate mofetil was added to a regimen consisting of ciclosporin for microemulsion and corticosteroids. The use of basiliximab in a triple therapy regimen including azathioprine or mycophenolate mofetil did not increase adverse events or infections in the basiliximab group as compared to placebo (see section 4.8).

 

4.6 Fertility, pregnancy and lactation